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Tartrazine was given in the diet to provide levels of 0% (control), 0.05%, 0.15%, and 0.45% (approximately 83, 259, 773 mg/kg/day, respectively) from five weeks of age of the F0 generation to nine weeks of age of the F1 generation in mice, and selected reproductive and neurobehavioural parameters were measured. In movement activity of exploratory behaviour in the F0 generation, number of vertical activity was significantly increased in the middle-dose group in males. There were no adverse effects of tartrazine on either litter size, litter weight and sex ratio at birth. The average body weight of male offspring was significantly increased in the high-dose group and that of female offspring was significantly increased in the middle-dose group at birth. In behavioural developmental parameters, surface righting at PND 4 was significantly accelerated in the high-dose group in male offspring, and those effects were significantly dose-related in a trend test (P<0.01). Cliff avoidance at PND 7 was significantly accelerated in the middle-dose group in male offspring. Negative geotaxis at PND 4 was significantly delayed in the high-dose group in female offspring. Other variables measured showed no significant adverse effects in either sex in the lactation period. In movement activity of exploratory behaviour in the F1 generation, number of movement showed a significant tendency to be affected in the treatment groups in male offspring in a trend test (P<0.05). The dose level of tartrazine in the present study produced a few adverse effects in neurobehavioural parameters during the lactation period in mice. Nevertheless, the high-dose level were in excess of the ADI of tartrazine (0-7.5 mg/kgbw), and the actual dietary intake of tartrazine is presumed to be much lower. It would therefore appear that the levels of actual dietary intake of tartrazine is unlikely to produce any adverse effects in humans.

A major purpose of the present studies was to determine the effects of varying the relative frequency, or bias, of stimulus presentation at different locations in a five-choice serial reaction time attention task. Training sessions were conducted in which the stimulus duration was held constant at 2 s and, initially, stimuli were presented with equal probability above each of the levers. During testing sessions, however, stimulus duration was either 0.2 or 2 s, and the frequency of presentation was varied among no bias, a middle bias, a left bias or a right bias condition. The training conditions were then changed such that the frequency of presentation was always a left bias, and test sessions were again conducted with no, middle, left or right bias. In the presence of the 0.2-s, but not the 2.0-s, stimulus, the percentage of correct responding on each of the choice levers during test sessions varied directly with the bias conditions in that the percentage of correct responding was highest at the most frequently presented location and lowest at the least frequently presented location. In addition, scopolamine, but not metscopolamine, increased omissions while also increasing anticipatory responses in rats trained under left-bias conditions and tested under right-bias conditions. The present findings suggest that varying the frequency of stimulus location can provide additional measures of attention in the five-choice serial reaction time task.

We studied the neurotropic effects of ACTH(4-10) analog semax against the background of dopaminergic receptors blockade with haloperidol. Intranasal administration of semax (0.05, 0.2, and 0.6 mg/kg) produced virtually no effect on disturbances of orientation and exploratory reactions and motor activity caused by intraperitoneal injection of 0.2 mg/kg haloperidol. By contrast, preliminary administration of 0.05 mg/kg semax prevented haloperidol-induced disturbances in active avoidance conditioning.

Objectives: The study investigated the effect of hormone replacement therapy (HRT) on cognitive processes in healthy, naturally postmenopausal women., Method: Participants were 64 volunteer postmenopausal women (27 in HRT, 37 in non-HRT group). Groups were matched for age, level of education and postmenopausal period. Duration of HRT was more than 12 months. Cognitive processes were measured through 44 scores obtained from Wechsler Memory Scale-Revised, Line Orientation Test, Cancellation Test and Raven Standard Progressive Matrices. All of these tests had been studied with respect to their psychometric properties in the Turkish culture [for review, Karakaş S. BILNOT battery: research and development of neuropsychological tests. Ankara, Turkey: Dizayn Ofset; 2004]., Results: Multivariate analysis of variance was performed where HRT and estradiol level were predictive (independent) variables and test scores were predicted (dependent) variables. The studied variables did not have a significant effect on a broad spectrum of neuropsychological scores that measured immediate and delayed visual and verbal memory, visuospatial perception and orientation, sustained attention/vigilance, visual search and scan, impulsivity and response speed, executive functions and general intelligence. Logistic regression analysis demonstrated a prediction rate of 86.89% of HRT status; the model was, however, based on four scores whose scientific relevance could not at this point be ascertained., Conclusion: The research design of the present observational study applied control techniques to demographic (age, level of education), menopausal (length of menopausal period, duration of HRT), and hormonal variables. The cognitive changes that some studies found concerning the effect of replacement therapy could not be found when the potentially confounding variables were thus controlled.

Several preattentive mechanisms have proved to be sensitive markers of clinical change in schizophrenia. Two related studies of visuospatial orientation used cued target detection combined with choice reaction time, short/long preparation, with or without a signal/target interval ("gap"/ "no-gap," to detect attentional disengagement difficulty in schizophrenia). End points were reaction times, alertness scores, attentional cost/benefit, and validity scores. Study 1, in 13 schizophrenics receiving second-generation antipsychotics and 13 controls, found the same impairment of disengagement as with neuroleptics, but intact reaction times and processing speed, with no hemispheric asymmetry. Study 2, in 12 untreated acute schizophrenics and 12 controls, showed slower reaction times, near-zero alertness in the fixation release condition, and impaired valid/invalid discrimination versus Syndrome Scale disorganization subscore (r = -0.81; P < 0.01). Early deficits in the preattentive orientation and visual. Early deficits in the preattentive orientation and visual detection phases are useful for assessing response to psychotropic treatment and establishing clinical correlates in acute schizophrenia.

Although nicotine and ethanol are often used together, little is known about their combined effects on visual system electrophysiology. This experiment examined the separate and combined effects of nicotine and ethanol on flash-evoked potentials (FEPs) recorded from both the visual cortex (VC) and superior colliculus (SC) of chronically implanted male Long-Evans rats. There were four treatment conditions administered on separate days: either saline or ethanol (2.0 g/kg, i.p.) was given 10 min before either saline or nicotine (1.0 mg/kg, s.c.). FEPs were recorded at 5, 20, and 40 min following the second injection. In the VC, ethanol significantly decreased the amplitude of most components, but increased P46. Peaks P22 and N53 were unchanged. Nicotine enhanced most component amplitudes, but decreased N29 and P234, while P22 and N139 were unchanged. In the SC, ethanol depressed the amplitude of all components studied. In contrast, nicotine significantly depressed only P27 and N48. Latencies of most components in both structures were increased by ethanol, nicotine, and the combination treatment, although a nicotine-induced enhancement of the effects of ethanol on latencies was not typically observed. Each drug treatment also produced significant hypothermia, with the combination treatment resulting in the greatest hypothermia. Ethanol, either alone or in combination with nicotine, significantly reduced body movements during the FEP recording sessions. In subsequent open-field observations, ethanol, but not nicotine, significantly increased the number of squares crossed, while the combination treatment produced the greatest increase in movement. Nicotine significantly increased rearing behavior, but both ethanol and the combination treatment eliminated rearings. Overall, data suggesting that nicotine can counteract some of the effects of ethanol was demonstrated in varying degrees in the amplitude of VC components N39, P46, N53, N65, and P88, the latency of VC component N53, the amplitude of SC component N59, and the latency of SC components N48 and N54. In contrast, a nicotine-induced enhancement of the effects of ethanol was found for only the latency of VC components N39, P88, and P234, body temperature, and open-field ambulation.

Prior studies have documented greater impairments in driving performance and greater alcohol consumption among adults with attention-deficit/hyperactivity disorder (ADHD). This study examined whether alcohol consumption produces a differentially greater impairment in driving among adults with ADHD in comparison to a community control group. The present study compared 50 adults with ADHD (mean age 33 years) and 40 control adults (mean age 29 years) on the effects of 2 single, acute doses of alcohol (0.04 and 0.08 blood alcohol concentration) and a placebo on their driving performance. The authors used a virtual reality driving simulator, examiner and self-ratings of simulator performance, and a continuous performance test (CPT) to evaluate attention and inhibition. Approximately half of the adults in each group were randomized to either the low or high dose alcohol treatment arms. Alcohol consumption produced a greater impact on the CPT inattention measures of the ADHD than the control group. Similar results were obtained for the behavioral observations taken during the operation of the driving simulator. Driving simulator scores, however, showed mainly a deleterious effect of alcohol on all participants but no differentially greater effect on the ADHD group. The present results demonstrated that alcohol may have a greater detrimental effect on some aspects of driving performance in ADHD than control adults.

In this study, we compared the effects of MK-801 and hippocampal lesions on re-training of Morris water maze place task in familiar and novel environments in rats. In Experiment 1, rats were pre-trained with the place task. After acquiring the task, rats were re-trained with the same task in a familiar environment following MK-801 injection, and were then trained with the same task in a novel environment following MK-801 injection. In the familiar environment, MK-801 had no effect, but in the novel environment performance was impaired. In Experiment 2, after the place task training, the hippocampus was lesioned, and rats were re-trained with the same task in the familiar environment then retrained again in the novel environment. Rats showed severe impairment in both environments. These two experiments suggest different functions for NMDA receptors and the hippocampus. The results of Experiment 1 showed that NMDA receptors are not required for utilizing spatial representations but they play an important role in the construction of spatial representations. The results of Experiment 2 show that the hippocampus is necessary for both the utilization of spatial representations already formed and the formation of new spatial representations.

Earlier studies found that recognition memory for object-place associations was impaired in patients with relatively selective hippocampal damage (Vargha-Khadem et al., Science 1997; 277:376-380), but was unaffected after selective hippocampal lesions in monkeys (Malkova and Mishkin, J Neurosci 2003; 23:1956-1965). A potentially important methodological difference between the two studies is that the patients were required to remember a set of 20 object-place associations for several minutes, whereas the monkeys had to remember only two such associations at a time, and only for a few seconds. To approximate more closely the task given to the patients, we trained monkeys on several successive sets of 10 object-place pairs each, with each set requiring learning across days. Despite the increased associative memory demands, monkeys given hippocampal lesions were unimpaired relative to their unoperated controls, suggesting that differences other than set size and memory duration underlie the different outcomes in the human and animal studies., ((c) 2005 Wiley-Liss, Inc.)

Recent pharmacological studies in animals and neuroimaging studies in normal humans suggest that the spatial and nonspatial cues in tasks measuring reflexive attention may be modulated by different neurotransmitter systems. The efficiency with which attention is oriented to explicit spatial cues may be altered by manipulating levels of brain acetylcholine, whereas reactions to nonspatial cues may be influenced by altering brain noradrenaline levels but not acetylcholine levels. In humans, however, previous attention studies have implicated dopamine when either explicit or implicit cueing is used. Some of the differences between animal and human work may be due to inadequate testing of nonspatial cues. To remedy this, we tested adult humans with ADHD that were primarily inattentive (ADHD/I) or combined inattentive/hyperactive (ADHD/C) and controls with the Attention Network Task that assesses both reflexive and voluntary attention and explicitly tests nonspatial cueing. Our results showed that spatial orienting in both subtypes was no different than controls. However, ADHD/C but not ADHD/I subjects had significantly slowed response times to nonspatial cues and cues with spatial conflict. Stimulant medication in a subset of ADHD/C subjects reduced these deficits to control levels. Based on these results, we conclude that ADHD/C subjects orient the focus of their attention normally but are impaired in their reactions both to abrupt visual cues and those that contain conflicting spatial cues.

Aims: The aim of this study was to determine neuropsychological performance in apparently cognitively, mentally, and physically healthy abstinent alcohol-dependent subjects compared with control subjects who were recruited for a number of different neuroimaging studies., Methods: All subjects completed a battery of neuropsychological tests as part of the neuroimaging protocol., Results: The group dependent on alcohol performed as well as controls on a non-verbal memory test and verbal fluency but performed worse in the verbal memory task, Trail A + B, and total IQ derived from Silverstein's short-form of the WAIS-R. However, the IQ performance of both groups was above average. In both groups, age was associated with slower performance on the Trail A + B task. In the alcohol-dependent group, severity of dependence and length of abstinence was not associated with performance of any task., Conclusions: In this apparently clinically healthy population of abstinent alcohol-dependent subjects, frontal lobe dysfunction was detectable using the Trail A + B and digit symbol tasks. This was despite above-average WAIS-R IQ scores. Consideration needs to be given to routine incorporation of cognitive testing in alcohol dependence since subtle deficits may not be easily apparent and may impact on treatment outcome.

Aims: To assess whether cognitive biases for drug-related cues are associated with subjective craving and behavioural indices of drug-seeking behaviour, as predicted by incentive models of addiction., Methods: Fifty social drinkers took part in a laboratory study in which their subjective craving and cognitive biases for alcohol cues were assessed, before they completed a progressive ratio operant task for alcohol (beer) reinforcement., Results: Social drinkers with high levels of alcohol craving at the beginning of the experiment had more pronounced attentional, approach, and evaluative biases for alcohol cues, compared with those with low craving. There were also trends for the high craving group to show greater operant responding for beer reinforcement, but the latter findings were inconclusive, and no evidence was found of associations between the operant responding and cognitive bias measures., Conclusions: The finding of a relationship between subjective craving and cognitive biases for alcohol cues is consistent with incentive models of addiction. Methodological factors may have obscured the predicted relationships between cognitive bias and operant performance, such as the use of a specific reinforcer (beer) during the operant task, while a range of alcohol-related cues were used in the cognitive bias tasks.

The novel human differentiating factor peptide fragment HLDF6 (Thr-Gly-Glu-Asn-His-Arg) was synthesized and purified. HLDF6 (0.1mg/kg i.p. but not 1mg/kg i.p.) improved not only long-term (24h) memory in adult rats in the water maze behavioural paradigm but also performance in the delayed matching-to-position (DMTP) task (0.3 and 1.0 but not 0.1mg/kg i.p). Hence, HLDF6 not only enhanced allocentric spatial learning and reference memory (water maze) but also improved temporal, spatial and working memory processes in the DMTP behavioural paradigm. Immunoreactivity blotting analysis of HLDF (the protein precursor of HLDF6) was performed and the following rank order of visual intensities from brain structures was noted: hippocampus cerebral cortex cerebellum hypothalamus striatum. Subsequently, we found that the highest absolute levels of HLDF were expressed in the hippocampus and cerebral cortex as detected by ELISA. We also demonstrated that HLDF6 enhanced [(3)H]-thymidine and [(14)C]-leucine incorporation into whole brain and hippocampal homogenates (maxima occurring within the range 10 (-12)-10 (-6) M) suggesting that this hexapeptide promoted de novo DNA and protein biosynthesis. We discuss this data in terms of their implications for links with other integrative metabolic pathways involving immediate early gene activation which may underpin a potential application for HLDF6 in limiting memory impairments associated with neurodegenerative diseases.

Rationale: The mesocortical dopamine system is regarded as an important modulator of working memory. While it has been established that stimulation of the D1/D2 receptor in primates can improve spatial working memory performance, findings in humans are less consistent. Recent studies in humans suggest that global depletion of dopamine via tyrosine/phenylalanine depletion may impair spatial working memory performance, although these results are also inconsistent, and it has been suggested that task differences may partly underlie the inconsistent findings., Objectives: This study had two aims: (1) to investigate the effects of acute tyrosine depletion (TPD) on a number of working memory tasks and (2) to examine whether stimulation of D1/D2 receptors under conditions of TPD can attenuate or "reverse" TPD-induced working memory impairments., Methods: Eighteen healthy male participants performed a spatial working memory delayed-recognition task, non-spatial working memory task and spatial n-back task on three separate occasions, after TPD, TPD and pergolide (D1/D2 agonist), and placebo., Results: TPD did not impair working memory performance on any of the tasks administered. However, stimulation of D1/D2 receptors under TPD conditions caused a subtle impairment in spatial working memory performance., Conclusions: The finding that D1/D2 stimulation under TPD conditions impairs working memory highlights the complexity of functional effects of augmenting dopaminergic transmission within a dopamine-depleted state. The lack of TPD-related effects on a range of working memory tasks questions the reliability of TPD as a modulator of dopamine function and working memory performance in humans.

Children with attention deficit hyperactivity disorder (ADHD) have been labeled as "inefficient movers"; however, little research has examined the effect of stimulant medication on lower extremity movements. 16 boys, 11 to 13 years old, with ADHD performed a lower-limb choice-response time task, both on and off medication. When nonmedicated, children had significantly slower reaction times to all three targets and significantly slower movement times for the contralateral and midline movements. For both conditions, children had significantly faster movement time when using the right leg than the left leg. These findings suggest that movement characteristics of children with ADHD are different under medicated and nonmedicated situations.

Rationale: Acetylcholine esterase (AchE) inhibitors are known to remediate symptoms of Alzheimer's disease. However, only few systematic data exist on the effects of cholinergic treatment on cognitive functions in normal subjects., Objective: This study evaluated the effects of donepezil, an inhibitor of AchE, on cognitive performance in young and healthy subjects., Methods: We used a randomised double-blind parallel group placebo-controlled repeated measures design to investigate changes of cognitive functions in a group of 30 young healthy male subjects (mean age 23.9 years+/-2.24 SD) upon application of donepezil or placebo for 30 days. Attentional and executive functions, visual and verbal short-term and working memory, semantic memory, as well as verbal and visual episodic memory were investigated using an extensive neuropsychological test battery., Results: Time-by-group interactions demonstrated significant drug effects that were specific to episodic memory in both the verbal and visual domain. Additionally, donezepil significantly improved long-term visual episodic recall. In none of the other functions under investigation any significant treatment effects were observed., Conclusion: Given this specific drug effect and the well-known relevance of the hippocampal region for episodic memory, we conclude that this region appears to be the major target of cholinergic enhancement in healthy subjects due to long-term inhibition of AchE.

Rationale: Discriminating right from left is an everyday cognitive ability. Repeated exposure to certain drugs, such as heroin, can produce poor performance on many cognitive tasks. However, it is yet unclear whether drug abuse impairs the ability of right-left discrimination., Objectives: The aim of the present study is to examine whether the spatial ability measured by the right-left discrimination task can be affected by heroin abuse and whether such drug effect, if it exists, is gender related., Methods: A paper-and-pen test was used. The test consists of line drawings of a person with no arm, one arm, or both arms crossing the vertical body axis of the figure. The line drawings are viewed from the back, from the front, or randomly alternating between the back and front drawings. The subjects' task is to mark which is the right or left hand in the figure as fast as possible., Results: A main finding in this study was that the ability to discriminate between left and right in visual space was impaired in heroin-dependent patients. Especially, heroin-dependent females performed poorer than control females in all conditions but heroin-dependent males only performed poorly in part of conditions., Conclusions: Recent heroin abuse impairs the ability of right-left discrimination and such impairment is gender related: heroin-dependent females demonstrated greater performance deficits than males.

Since the massive population decline of the long-spined sea urchin, Diadema antillarum, in the early 1980s, the dynamics of coral reef ecosystems in the Caribbean have changed tremendously. The absence of D. antillarum, once a keystone herbivore, has led to macroalgal dominance in many of these reef communities. D. antillarum is not only important ecologically, but may also be a sensitive bioindicator species for toxicant exposure. Echinoderm larval development tests were conducted with D. antillarum exposed to elevated levels of aqueous copper (Cu), silver (Ag), nickel (Ni), or selenium (Se). All metals significantly affected larval development, based on normal development to the pluteus stage. The EC50s based on dissolved metal concentrations were 11 microg/L Cu, 6 microg/L Ag, 15 microg/L Ni, and 26 microg/L Se. Adult sea urchins were exposed to aqueous copper under flow through conditions for 96 h. The 96-h LC50 for this exposure was 25 microg/L dissolved Cu. Additionally, behavioral and physiological disturbance was observed. The physiological responses included both acid-base balance disturbance, as evidenced by reduced coelomic fluid pH and apparent ionoregulatory effects. In addition, behavioral effects included spatial orientation within the exposure tank, spine closure, and loss of spines. The high sensitivity of both adult and larval D. antillarum to these metals supports the use of this organism as an important biological indicator for metal exposure in marine environments.

Aim: To investigate the effect of chronic morphine exposure on the receptive field properties of lateral geniculate nucleus (LGN) neurons in cats., Methods: Cats were injected with morphine (10 mg/kg) or saline twice daily, for 10 d. Subsequently, extracellular single-unit recording techniques were used to examine the sensitivity of LGN neurons to visual stimuli in chronic morphine-treated and saline-treated cats., Results: Compared with saline-treated cats (as controls), LGN neurons in morphine-treated cats had decreased signal-to-noise ratios (1.9 vs 3.1), and orientation and direction sensitivity (0.103 vs 0.135 and 0.074 vs 0.10, respectively), accompanied by significant increases in spontaneous (27.4 vs 17.5) and evoked activity (preferred: 42.2 vs 38.1; average: 28.1 vs 22.3)., Conclusion: Chronic morphine exposure can lead to the functional degradation of LGN neurons in cats, which might result from the effects of chronic morphine exposure on inhibitory neurotransmission.

Rationale: Attentional bias for drug-related cues has been reported with a wide range of drugs, but to date the extent to which caffeine consumers show similar biases for caffeine-related stimuli has not been tested. The present study therefore examined this issue in terms of differences in attentional bias for caffeine-related words in High, Moderate and Non-caffeine consumers using a dot-probe word task following overnight caffeine abstinence., Objectives: This study was conducted to test whether caffeine consumers show an attentional bias for caffeine-related words, and whether such biases relate to habitual levels of caffeine use., Methods: Sixteen High, Moderate and Non-consumers of caffeine were asked to complete a modified dot-probe task in order to measure attentional bias for caffeine-related relative to neutral control word groups. The task was completed following overnight caffeine abstinence, and participants also completed mood and caffeine-craving measures., Results: The High consumer group showed a significant attentional bias for the caffeine-related words, but no such bias was seen in Moderate or Non-consumer groups. As expected, craving for caffeine was strongest in the High consumers and weakest in the Non-consumers. Attentional bias in the High group correlated with self-reported caffeine consumption and with craving for caffeine, but neither effect was significant in the Moderate group., Conclusions: These data confirm that High caffeine consumers show attentional bias for caffeine-related stimuli, consistent with current theories of drug addiction.

There is now accumulating evidence that the striatal complex in its two major components, the dorsal striatum and the nucleus accumbens, contributes to spatial memory. However, the possibility that different striatal subregions might modulate specific aspects of spatial navigation has not been completely elucidated. Therefore, in this study, two different learning procedures were used to determine whether the two striatal components could be distinguished on the basis of their involvement in spatial learning using different frames of reference: allocentric and egocentric. The task used involved the detection of a spatial change in the configuration of four objects placed in an arena, after the mice had had the opportunity to experience the objects in a constant position for three previous sessions. In the first part of the study we investigated whether changes in the place where the animals were introduced into the arena during habituation and testing could induce a preferential use of an egocentric or an allocentric frame of reference. In the second part of the study we performed focal injections of the N-methyl-d-aspartate (NMDA) receptors' antagonist, AP-5, within the two subregions immediately after training. The results indicate that using the two behavioral procedures, the animals rely on an egocentric and an allocentric spatial frame of reference. Furthermore, they demonstrate that AP-5 (37.5, 75, and 150 ng/side) injections into the dorsal striatum selectively impaired consolidation of spatial information in the egocentric but not in the allocentric procedure. Intra-accumbens AP-5 administration, instead, impaired animals trained using both procedures.

Objective: Acute alcohol tolerance refers to the observation of reduced impairment at a given blood alcohol concentration (BAC) on the descending versus ascending limb of the blood alcohol curve. Psychomotor performance measures used in human studies of alcohol tolerance provide reliable assessments of tolerance but do not identify specific mechanisms involved in the re-establishment of control, and little is known about how acute tolerance is expressed in terms of changes in fundamental mechanisms that regulate and control behavior. This study examined the expression of acute alcohol tolerance to impaired behavioral control in terms of changes in a drinker's ability to activate and inhibit behavioral responses as BAC ascended and declined following a dose., Method: Twenty social drinkers performed a cued go/no-go task that measured behavioral control after receiving a moderate dose (0.65 g/kg) of alcohol and a placebo. The development of acute tolerance was measured by testing behavioral control twice: once during the ascending phase and again at comparable BACs during the descending phase of the blood alcohol curve., Results: Inhibitory and activational aspects of behavioral control both were impaired by alcohol. Acute tolerance developed to the impaired activation but not to the impaired inhibition of behavior., Conclusions: The results highlight the importance of considering behavioral requirements when testing for the development of acute tolerance under a dose of alcohol. By modeling behavioral control as the net effect of countervailing activational and inhibitory influences, the study suggests that fundamental mechanisms of control might not display uniform tolerance development.

Rationale: The central cholinergic system is implicated in cognitive functioning. The dysfunction of this system is expressed in many diseases like Alzheimer's disease, dementia of Lewy body, Parkinson's disease and vascular dementia. In recent animal studies, it was found that selective cholinergic modulation affects visuospatial processes even more than memory function., Objective: In the current study, we tried to replicate those findings. In order to investigate the acute effects of cholinergic drugs on memory and visuospatial functions, a selective anticholinergic drug, biperiden, was compared to a selective acetylcholinesterase-inhibiting drug, rivastigmine, in healthy elderly subjects., Methods: A double-blind, placebo-controlled, randomised, cross-over study was performed in 16 healthy, elderly volunteers (eight men, eight women; mean age 66.1, SD 4.46 years). All subjects received biperiden (2 mg), rivastigmine (3 mg) and placebo with an interval of 7 days between them. Testing took place 1 h after drug intake (which was around Tmax for both drugs). Subjects were presented with tests for episodic memory (wordlist and picture memory), working memory tasks (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Visuospatial abilities were assessed by tests with high visual scanning components (tangled lines and Symbol Digit Substitution Test)., Results: Episodic memory was impaired by biperiden. Rivastigmine impaired recognition parts of the episodic memory performance. Working memory was non-significantly impaired by biperiden and not affected by rivastigmine. Motor learning as well as visuospatial processes were impaired by biperiden and improved by rivastigmine., Conclusions: These results implicate acetylcholine as a modulator not only of memory but also of visuospatial abilities.

Rationale: Ultra-low-dose opioid antagonists enhance opiate analgesia and attenuate tolerance and withdrawal., Objectives: To determine whether ultra-low-dose naltrexone (NTX) coadministration alters the rewarding effects of opiates or the aversive effects of opiate withdrawal., Methods: We used the conditioned place preference (CPP) and conditioned place aversion (CPA) paradigms to assess whether ultra-low-dose NTX alters the acute rewarding effects of oxycodone or morphine, or the aversive aspect of withdrawal from either drug. To assess the dose response for ultra-low-dose NTX, a range of NTX doses (0.03-30 ng/kg) was tested in the oxycodone CPP experiment. In order to avoid tolerance or sensitization effects, we used single conditioning sessions and female rats, as females are more sensitive to the conditioning effects of these drugs., Results: Ultra-low-dose NTX (5 ng/kg) blocked the CPP to morphine (5 mg/kg) and the CPA to withdrawal from chronic morphine (5 mg/kg, for 7 days). Coadministration of ultra-low-dose NTX (30 pg/kg) also blocked the CPA to withdrawal from chronic oxycodone administration (3 mg/kg, for 7 days). The effects of NTX on the CPP to oxycodone (3 mg/kg) revealed a biphasic dose response. The two lowest doses (0.03 and 0.3 ng/kg) blocked the CPP, the middle dose (3 ng/kg) was ineffective, and oxycodone combined with the highest dose (30 ng/kg) produced a trend toward a CPP., Conclusions: Ultra-low-dose NTX coadministration blocks the acute rewarding effects of analgesic doses of oxycodone or morphine as well as the anhedonia of withdrawal from chronic administration.

Background: Repeated ethanol treatment has been reported to differentially affect water maze performance in adolescent and adult rats. The present study was undertaken to determine the age-specific reversal of ethanol-induced deficit in water maze performance., Methods: Adolescent and adult male rats were subjected to repeated ethanol or saline treatments. Experimental rats were injected daily with 2 g/kg ethanol (intraperitoneally) for five consecutive days (Days 1-5) and tested in the hidden platform task of the Morris water maze 30 minutes after ethanol treatment; control rats received isovolumetric saline. On the last training day, all rats were tested in the probe trial and in the cued visual task. After an ethanol-free period of 4-25 days, rats were retested in the water maze., Results: Adolescent ethanol-treated rats had significantly higher latencies and swam greater distances to find the hidden platform, compared to age-matched saline control rats. Ethanol rats also showed increased hug time, i.e., spent significantly more time near the periphery of the pool than control rats. In the probe trial, compared to adolescent saline rats, ethanol rats spent less time in the target quadrant. However, there was no difference between ethanol- and saline-treated rats in the swim speed or in the visual task performance. Experimental and control rats were retested in the water maze 4 days (Day 9), 7 days (Day 12), and 25 days (Day 30) after the last ethanol/saline treatment; no injections were given on those days. Ethanol-treated rats continued to do poorly on all retest days. Ethanol treatment in adult male rats acutely increased latency and distance to find the hidden platform, but unlike adolescent alcohol rats, their performance in the probe trial did not differ from adult saline rats. Also, swim speed and visual task performance of adult rats were significantly affected by ethanol exposure. During retesting, their performance did not differ from adult control rats., Conclusions: Adolescent rats exposed to ethanol showed deficits in water maze performance, had increased hug time, and failed to catch up with control rats during the weeks after the ethanol treatment period was over. Adult alcohol rats showed some behavioral dysfunction (increased latency and distance to find the hidden platform) but had problems swimming, and in the probe trial they performed as well as control rats. Also, in adult rats, ethanol-induced impairments were quickly reversed after the ethanol treatment was over, a finding that suggests impaired motor coordination more than a true learning deficit. Together, these data indicate that repeated ethanol treatment in adolescent rats, but not adult rats, show long-term impairments in maze performance.

The effect of panavir on Parkinson's syndrome induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine was studied in C57Bl/6 mice and outbred albino rats. Two injections of panavir significantly reduced the severity of oligokinesia and autonomic manifestations of experimentally induced Parkinson's syndrome.

Human exposures to acrylamide (ACR), a known neurotoxicant, can occur via a variety of substances, including cigarette smoke and the ingestion of certain carbohydrate-based foods cooked at high temperatures. In this study, Fischer 344 sperm plug-positive female rats were treated daily with ACR (0, 0.5, 1.0, 2.5, 5.0 or 10.0 mg/kg/day) by gavage beginning on gestation day 7. Dosing of dams ended when litters were born; pups received daily gavage at the same dose as their dam from postnatal day (PND) 1 through PND22. Pups were tested using a battery of behavioral assessments from PNDs 4-22. Statistically significant decreases in body weight were observed in pups exposed to ACR at doses as low as 1.0 mg/kg/day (treatmentxday; repeated measures ANOVA, P<0.0001). No statistically significant differences among treatment groups were observed in righting reflex, forelimb hang, or open field measures of activity. Statistically significant effects of ACR were observed at the 10 mg/kg/day dose on negative geotaxis performance (P<0.01) and a linear trend in fall-time latencies on Rotarod performance on PNDs 21-22 (P<0.05), with higher doses producing shorter latencies. These results suggest that ACR exposure produces deficits in development and motor coordination that are observable before weaning.

Adult rats (prenatally methamphetamine-exposed, saline-exposed and controls) were tested for learning in the Morris water maze. Rats were tested in 4 consecutive days using two different types of learning tests: "Place navigation test" (stable platform position) and "New-learning test" (platform position changed daily). Males exposed prenatally to methamphetamine were slower in the Place navigation learning test than were both the control and saline-exposed males. There were no differences in the New-learning test between groups.

The effect of phenibut on the locomotor and orientation-research activity, as well as on the alcohol and food motivation, was studied on experimental animals under conditions of voluntary chronic alcoholism. Phenibut decreased the manifestations of alcohol-induced behavioral disorders and reduced alcohol motivation.

Spatial cognition appears to be compromised in elderly and in patients suffering from dementia. These deficits are believed to be modelled, at least partly, by the administration of scopolamine or MK-801 in normal adult animals. In order to establish an animal model suited for the evaluation of putative cognition enhancers, we assessed the effects of scopolamine (0.3, 0.5, 0.7 mg kg(-1), i.p.) and MK-801 (0.07, 0.08, 0.09 mg kg(-1), s.c.) in rats trained in the cone field. This task allows the simultaneous investigation of working memory (WM), reference memory (RM) and search strategies. Scopolamine and MK-801 reliably induced spatial cognition deficits in the cone field without inducing behavioural side effects. This task appears to be suited for assessing the effects of putative cognition-enhancing compounds on spatial cognition.

Spatial orientation is considered to be an animal model of human cognitive functions. Efficient navigation is believed to require a brain representation of the environment. The role of NMDA-receptor-dependent neurotransmission in encoding spatial representations has been intensively studied; however, its involvement in organizing spatial information into neural representations is poorly understood. We tested the effect of NMDA-receptor blockade on the performance of rats in Active Allothetic Place Avoidance (AAPA), a cognitive task which requires rats to separate two conflicting spatial reference frames (room and arena frames), when only the room frame is relevant for solution of the task. The NMDA-receptor blockade was achieved by systemic administration of either 0.15 mg/kg or 0.2 mg/kg of dizocilpine (MK-801), a non-competitive NMDA-receptor antagonist. Two distinct AAPA setups located in different rooms were used. The rooms had different layouts of robust extramaze landmarks. Intact rats were trained in the upstairs arena and, subsequently, they received saline or MK-801 and their performance was tested (reinforced retention). Re-acquisition of AAPA task in the downstairs room was then tested under saline or MK-801. MK-801 at the dose of 0.2 mg/kg was found to disrupt the reinforced retention of the AAPA. Re-acquisition of AAPA in the novel environment was impaired by both doses of MK-801. Taken together, administration of MK-801 causes an orientation deficit in the AAPA task irrespectively of the rats' prior intact pretraining. These results support the hypothesis that NMDA-receptors play a pivotal role in cognitive processes.

Prior studies in animals and humans indicate that reorienting of visuospatial attention is modulated by the cholinergic agonist nicotine. We have previously identified neural correlates of alerting and reorienting attention in humans and found that the parietal cortex is specifically involved in reorienting. This study investigates whether the alerting and reorienting systems, especially in the parietal cortex, are modulated by nicotine. We used event-related functional magnetic resonance imaging (fMRI) and studied 15 nonsmoking volunteers under placebo and nicotine (NICORETTE) polacrilex gum 1 and 2 mg). Subjects performed a cued target detection task with four different types of randomly intermixed trials (no, neutral, valid, and invalid cue trials). Alerting was captured by comparing BOLD activity and reaction times (RTs) in neutrally cued trials with no cue trials. Reorienting was isolated by comparing invalidly with validly cued trials. On the behavioral level, nicotine affected reorienting of attention by speeding RTs in invalidly cued trials; alerting was not affected by nicotine. Neurally, however, nicotine modulated both attentional systems. Pharmacologic effects on alerting-related brain activity were mainly evident as modulation of BOLD responses in the right angular gyrus and right middle frontal gyrus due to a reduction of neural activity in no cue trials. In the reorienting system, effects of nicotine were mainly evident in the left intraparietal sulcus and precuneus and due to a reduction of neural activity in invalidly cued trials. We conclude that nicotine enhances reorienting of attention in visuospatial tasks and that one behavioral correlate of speeded RTs is reduced parietal activity.

Chlorpyrifos-methyl, a wide-spectrum organophosphorus insecticide and potential toxic pollutant contaminating aquatic ecosystems, was investigated for acute toxicity. Larvae of the freshwater fish Nile tilapia (Oreochromis niloticus L.) were selected for the bioassay experiments. The experiments were repeated three times and the 96 h LC50 was determined for the larvae. The static test method for assessing acute toxicity was used. Water temperature was maintained at 25+/-1 degrees C. In addition, behavioral changes at each chlorpyrifos-methyl concentration were observed for the individual fish. Data obtained from the chlorpyrifos-methyl acute toxicity tests were evaluated using Finney's probit analysis statistical method. The 96 h LC50 value for Nile tilapia larvae was calculated to be 1.57 mg/l.

Rationale: Features of childhood attention-deficit/hyperactivity disorder (ADHD) often persist into adulthood. It has been shown that adult ADHD is associated with various neurocognitive deficits, including impairments in spatial working memory (SWM) and attention. It is not known whether these deficits are ameliorated by methylphenidate in adult ADHD., Objectives: The aim of this study was to evaluate the neurocognitive effects of a single dose of methylphenidate on SWM, visual memory, spatial span and sustained attention in adult ADHD., Methods: Twenty-four adult patients, recruited from a specialised clinic for the assessment of adult ADHD, were entered into a double-blind, randomised, placebo-controlled crossover study using a single 30 mg dose of methylphenidate., Results: Eighteen patients met DSM-IV criteria for adult ADHD. Methylphenidate resulted in an improvement in SWM performance and sustained attention, together with a speeding in response time, in these patients. Six patients with attentional difficulties, who did not meet a DSM-IV diagnosis of ADHD, showed a different pattern of response to methylphenidate compared to the ADHD group. For the combined group, moderate correlations were shown between childhood ratings of ADHD (both self-reported and informant ratings) and response to methylphenidate on the SWM task., Conclusions: Adults with ADHD had a similar neurocognitive response to methylphenidate to that previously reported for childhood ADHD. Our results provide further support for the validity of the ADHD syndrome as defined by DSM-IV and indicate possible neurocognitive substrates for clinical improvement with chronic methylphenidate.

Fetal alcohol syndrome (FAS) is a major cause of learning and sensory deficits in children. The visual system in particular is markedly affected, with an elevated prevalence of poor visual perceptual skills. Developmental problems involving the neocortex are likely to make a major contribution to some of these abnormalities. Neuronal selectivity to stimulus orientation, a functional property thought to be crucial for normal vision, may be especially vulnerable to alcohol exposure because it starts developing even before eye opening. To address this issue, we examined the effects of early alcohol exposure on development of cortical neuron orientation selectivity and organization of cortical orientation columns. Ferrets were exposed to ethanol starting at postnatal day (P) 10, when the functional properties and connectivity of neocortical neurons start to develop. Alcohol exposure ended at P30, just before eye opening at P32. Following a prolonged alcohol-free period (15-35 days), long-term effects of early alcohol exposure on cortical orientation selectivity were examined at P48-P65, when orientation selectivity in normal ferret cortex has reached a mature state. Optical imaging of intrinsic signals revealed decreased contrast of orientation maps in alcohol- but not saline-treated animals. Moreover, single-unit recordings revealed that early alcohol treatment weakened neuronal orientation selectivity while preserving robust visual responses. These findings indicate that alcohol exposure during a brief period of development disrupts cortical processing of sensory information at a later age and suggest a neurobiological substrate for some types of sensory deficits in FAS.

The location of distant resources using odor information usually also requires information on the flow of air (or water) through the environment together with the expression of internally programmed steering responses. The orientation responses of virgin male Periplaneta americana L. to wind and the female sex-pheromone component (-)-periplanone-B were video-recorded in a laboratory wind tunnel and quantified. P. americana males showed no preferred walking orientation when released in zero wind in the absence of pheromone. When introduced into 25 cm s(-1) wind in the absence of pheromone, 79% of males walked downwind. Upon introduction to a plume of (-)-periplanone-B in wind, 100% of males walked upwind in the pheromone plume to the source. Males were then challenged with wind-borne plumes of (-)-periplanone-B of four different temporal/spatial structures. In nearly all cases, the only statistically significant changes in behavioral parameters measured from their walking tracks were observed from males tracking the treatment consisting of the most turbulent plume. The plume-tracking performances of males challenged with the other three less turbulent plumes were visually and quantitatively similar, regardless of the width. Males tracking all four plumes showed evidence of turns resulting from multiple mechanisms. Some of the observed maneuvers were temporally regular counterturns, suggesting steering according to an ongoing internal program, while others could have been triggered by encountering the change in odor concentration between pheromone and clean air at the lateral boundary of the plume or chemotactically upon the detection of changes in odor concentration.

The aim of these experiments was to assess whether the clinically validated cognition enhancers donepezil (Aricept, E2020) and metrifonate antagonize scopolamine-induced deficits in the cone field, a complex spatial discrimination task. The cone field task allows measurement of the effects of experimental manipulations on working and reference memory (WM and RM), search strategies, and on the speed and latency to execute the task. The effects of a single administration of donepezil (0.1, 0.3, and 1.0 mg kg(-1), p.o.) and metrifonate (30, 60, and 120 mg kg(-1), p.o.) were investigated in adult Harlan-Wistar rats trained to a stable level of performance and pretreated with scopolamine (0.5 mg kg(-1), i.p. 30 min before training). Scopolamine impaired WM without inducing overt non-cognitive side-effects. Donepezil did not antagonize the scopolamine-induced deficits, whereas metrifonate antagonized the WM deficits at the dose of 60 mg kg(-1), but not at 30 or 120 mg kg(-1). Thus, a cholinesterase inhibitor with proven clinical efficacy can antagonize scopolamine-induced spatial memory deficits. The cone field would be a useful component of a behavioral screening battery to test the effects of putative cognition enhancers.

We have shown previously that phenytoin impairs learning in rats in several different behavioral paradigms (Churchill et al., 1998, 2003; Banks et al., 1999). The present study has examined this drug's effects on performance in a delayed match-to-place water maze paradigm developed by Steele and Morris (1999). We find that phenytoin retards performance, but only when the inter-trial interval (ITI) is short (i.e., 15-sec). With longer ITIs (i.e., 20-min, 2-hr), the performance of the phenytoin-treated rats was quite comparable to the controls. We suggest that this pattern of results stems from a disruption of spatial working memory, perhaps due to the effects of the drug on hippocampal function (cf., Churchill et al., 1998, 2003). This disruption is, however, not so profound that consolidation is prevented.

The hippocampus is critical for navigation in an open field. One component of this navigation requires the subject to recognize the target place using distal cues. The experiments presented in this report tested whether blocking hippocampal function would impair open field place recognition. Hungry rats were trained to press a lever on a feeder for food. In Experiment 1, they were passively transported with the feeder along a circular trajectory. Lever pressing was reinforced only if the feeder was passing through a 60 degrees -wide sector. Thus, rats preferentially lever pressed in the vicinity of the reward sector indicating that they recognized its location. Tetrodotoxin (TTX) infusions aimed at the dorsal hippocampi caused rats to substantially increase lever pressing with no preference for any region. The aim of Experiment 2 was to determine whether the TTX injections caused a loss of place recognition or a general increase of lever pressing. A separate group of rats was conditioned in a stationary apparatus to press the lever in response to a light. The TTX injections did not abolish preferential lever pressing in response to light. Lever pressing increased less than half as much as the TTX-induced increase in Experiment 1. When these animals with functional hippocampi could not determine the rewarded period because the light was always off, lever pressing increased much more and was similar to the TTX-induced increase in Experiment 1. We conclude that the TTX inactivation of the hippocampi impaired the ability to recognize the reward place., ((c) 2005 Wiley-Liss, Inc.)

The role of short-chain fatty acids in the host-seeking behaviour of Triatoma infestans larvae was investigated using a locomotion compensator. Several short-chain fatty acids were tested alone over a wide range of doses, or in combination with L-lactic acid (L-LA; 100 microg). Bugs showed no attractive response to single carboxylic acids, but when L-LA was added to airstreams carrying specific intensities of either propionic (C3; 100 microg), butyric (C4; 1 microg) or valeric acid (C5; 1 microg), these mixtures elicited an attractive response, evincing a synergistic effect. No orientation response was observed when caproic acid (C6) was offered with L-LA at the doses tested. Two blends were created: (1) C3, C4 and C5 combined at the effective doses when added with L-LA [C3C4C5 (1)], and (2) C3, C4 and C5 combined at a third of those intensities [C3C4C5 (2)]. Both blends were tested alone, with L-LA (100 microg), with a sub-threshold concentration of CO(2) (300 p.p.m. above the ambient level), and combined with both compounds together. Oriented responses of bugs were only observed with the blend (2) added with L-LA and with the combination of this lure with CO(2). This last combination evoked a behavioural response similar in intensity to that induced by a live mouse.

It has been shown that schizophrenic patients treated with conventional neuroleptics display a general slowness in latency in simple reaction-time tasks and a disengagement deficit in visual-orienting tasks. Yet, the influence of atypical neuroleptics on attention is still controversial. The purpose of our study was to investigate the effect of atypical neuroleptics in tasks requiring alertness, selective attention or visual orienting. Thirteen stabilized schizophrenic patients receiving atypical neuroleptics were compared to 13 healthy controls matched for age, gender, and study level, in a choice reaction time (CRT) task and a visual-orienting task cued target detection (CTD) task. The results showed that patients and controls obtained comparable reaction times (RTs) in the CRT task. In the CTD task, both groups had comparable RTs but the presence of invalid cues caused a greater attentional cost in both visual fields for patients compared to controls, indicating a symmetrical disengagement deficit. To conclude, patients treated with atypical neuroleptics had a phasic alertness ability similar to controls. By contrast, an impairment of disengagement was present in those patients. Thus, atypical neuroleptics could have a positive influence on certain but not all attentional domains.

Tadpoles (Xenopus laevis) have a lateral line system whose anatomical structure has been described, but whose functional significance has not been closely examined. These experiments tested the hypothesis that the lateral line system is involved in rheotaxis. Tadpoles in developmental stages 47-56 oriented toward the source of a water current. Orientation was less precise after treatment with cobalt chloride or streptomycin, but was similar to that of untreated animals after exposure to gentamicin. In no current conditions, tadpoles exhibited a characteristic head-down posture by which they held themselves in the water column at an angle around 45 degrees. This body posture became significantly less tilted in the presence of water current. Treatment with cobalt chloride or streptomycin increased the angle of tilt close to that seen in no current conditions, while gentamicin treatment tended to decrease tilt angle. The data are consistent with anatomical and physiological findings that tadpole neuromasts are similar to superficial, but not canal, neuromasts in fishes, and they suggest that the lateral line system is involved in both directional current detection and current-related postural adjustments in Xenopus.

Recently, it has been demonstrated that targeted blockade of the extracellular signal-regulated kinase (ERK) cascade in either the entorhinal cortex (EC) or hippocampus (HIP) results in spatial memory deficits. However, it is unclear if ERK-mediated plasticity in these structures has redundant functions or unique roles. In this report, we contrast the role of long-term plasticity in these two structures with side-by-side comparisons of the effects of PD098059 infusion following water maze training. Analysis of performance during the long-term retention test indicates a role for plasticity in the EC in storing broad location information. In contrast, blocking plasticity in the HIP resulted in deficits in indices of precise location information and goal-directed navigational error. To distinguish between a navigational and location deficit, a "two-room" experimental design was employed. Training in the first room allowed animals to consolidate information regarding navigational strategies prior to training and drug infusion in the second room. Hippocampal-PD098059-infused animals demonstrated behavior suggestive of an expanded representation of the platform location and, thus, a loss of precise location information, suggesting that plasticity in these structures is involved in nonredundant, but complementary, processes necessary for spatial memory.

The primary visual cortex of rats is surrounded laterally (in Oc2L) and medially (in Oc2M) by several peristriate visual areas. Previous studies from our laboratory demonstrated that bilateral lesions in Oc2L result in visual pattern discrimination deficit, and in failure to solve a conditional discrimination which requires figure-background association. In contrast, neurotoxic lesions of the rostral part of Oc2M (which contains the anteromedial and anterior peristriate visual areas, collectively referred to as AM complex) result in deficits in visuospatial discrimination, and in disruptions in visual tasks involving spatial memory. The objective of this study was to behaviorally test the role of AM complex in a spatial memory task in absence of visual cues. For this purpose, we analyzed memory retention of Lashley III maze in blind rats after bilateral ibotenate lesions in AM complex, or in the primary visual cortex (V1, Oc1), to test the hypothesis that AM complex is essential for this cognitive task. The results showed a significant loss of memory retention of the maze in rats with lesions in AM complex, but not in rats with lesions in V1. Furthermore, the retention loss in rats with AM complex lesions was positively and significantly correlated with the size of the lesion. The results indicate a critical role of AM complex in spatial memory mechanisms independent on visual cues. A probable homology of rat AM complex with the posterior parietal cortex of primates is discussed.

Homocystinuria is an inherited metabolic disease biochemically characterized by tissue accumulation of homocysteine. Affected patients present mental retardation and other neurological symptoms whose mechanisms are still obscure. In the present study, we investigated the effect of chronic hyperhomocysteinemia on rat performance in the Morris water maze task. Chronic treatment was administered from the 6th to the 28th day of life by s.c. injection of homocysteine, twice a day at 8-h intervals; control rats received the same volume of saline solution. Animals were left to recover until the 60th day of life. Morris water maze tasks were then performed, in order to verify any effect of early homocysteine administration on reference and working memory of rats. Results showed that chronic treatment with homocysteine impaired memory of the platform location and that homocysteine treated animals presented fewer crossings to the place where the platform was located in training trials when compared to saline-treated animals (controls). In the working memory task, homocysteine treated animals also needed more time to find the platform. Our findings suggest that chronic experimental hyperhomocysteinemia causes cognitive dysfunction and that might be related to the neurological complications characteristic of homocystinuric patients.

Four experiments with C57BL/6 mice examined the effects of protein synthesis inhibition on extinction of spatial preferences in the Morris water maze. The protein synthesis inhibitor anisomycin was injected systemically immediately after spatial reversal sessions, which consisted of eight, two, or one reversal trials. Anisomycin had no effect on extinction of a spatial preference with eight reversal trials per session. When only two reversal trials were administered per session, anisomycin slowed extinction initially, although full extinction occurred with further training even in the presence of anisomycin. In both cases, anisomycin blocked acquisition of the reversal preference. When anisomycin injections followed a single simple extinction trial, performance was not disrupted. These findings suggest that acquisition and extinction may involve different molecular processes, and they do not support the idea that brief extinction trials induce a protein synthesis-dependent reconsolidation phase of spatial memory.

The olfactory bulbectomised (OB) rat is being increasingly used as a model of impaired learning and mnemonic functioning. In this study the model has been utilised to determine the effect of the acetylcholinesterase inhibiting compounds tacrine and physostigmine on spatial working memory deficits associated with the OB rat. One-hundred and twenty male rats were randomly allocated to OB or sham operated groups and received chronic i.p. treatment with either saline, physostigmine (0.1 mg/kg) or tacrine (0.1 and 0.3 mg/kg). Two weeks after beginning treatment animals were tested on the Morris water maze and open field test. The results indicated that the OB surgery was associated with spatial working memory disturbances that were effectively attenuated with both doses of tacrine, but not physostigmine. Increased hyperactivity and defecation was observed in OB animals in the Open-field test, however, these changes were not ameliorated by either drug treatment. The ability for tacrine but not physostigmine to attenuate OB cognitive deficits may be associated with the different half-life of these compounds. This study provides further support for the use of the OB rat as a drug discovery model for the investigation of novel therapeutic compounds that target the cholinergic system.

Our previous study showed the microinjection of drugs that influence the nitric oxide (NO)-mediated neurotransmission in the hippocampus impacts upon the anxiolytic-like effect of ethanol. In this study, we examined whether NO-dependent pathways of the dorsolateral periaqueductal gray (dlPAG) participate in the anxiolytic effect of ethanol in rats submitted to the elevated plus-maze test. We evaluated the impact on ethanol effects of the nitric oxide synthase (NOS) inhibitor 7-nitroindazole, the soluble guanylate cyclase inhibitor 1H-(1,2,4)-oxodiazolo (4,3-a) quinoxalin-1-one (ODQ), the cyclic guanylate monophosphate (cGMP) analogue 8-bromo-cGMP and the NO donor sodium nitroprusside. The results showed that ODQ and 7-nitroindazole increased the percentage of open arm entries and of time spent on open arms in the elevated plus maze in rats injected with ethanol at 1.0g/kg, a dose that did not produce anxiolysis per se. Conversely, 8-bromo-cGMP and sodium nitroprusside blocked the increased exploration of open arms exhibited by rats treated with a higher dose of ethanol (1.2g/kg). Taken together, the results suggest that the inhibition of NO-dependent pathways of the dlPAG enhances the anxiolytic effect of ethanol, whereas the activation of these pathways results in an opposite effect.