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Aim The relationship between declining performance, as measured by changes in reaction time, and declining cognitive function has not been critically studied. The aim of the present study was to investigate the association between reaction time during a task and cognitive ability in elderly Taiwanese individuals. Methods Patients aged 65 years or older with mild cognitive impairment (MCI) (n = 33) and Alzheimer’s disease (n = 26) were recruited from the neurology clinic of a regional hospital in southern Taiwan. In addition, 28 healthy controls aged 65 years or older were recruited from the community. The cognitive performance of the study participants was assessed using the Cognitive Abilities Screening Instrument (CASI). A computer-administered simple reaction time (SRT) task and a flanker reaction time (FRT) task were administered to assess participants’ cognitive function. A non-parametric Kruskal–Wallis test was performed to compare CASI scores, SRT, and FRT among the three groups. anova was also used to compare CASI scores, inverse-transformed SRT, and inverse-transformed FRT among the three groups, with adjustment for age and years of education. Additionally, Pearson’s partial correlation coefficients were used to assess the association of CASI scores with inverse-transformed SRT, and inverse-transformed FRT within each of the three groups. Results Significant differences in CASI scores, SRT, and FRT were found between the Alzheimer’s disease group and the other two groups, either with or without adjustment for age or education. The reaction time of patients with Alzheimer’s disease was significantly slower than the other two groups. Moreover, significant correlation between CASI and FRT was found in patients with MCI. Conclusion Altered performance in a speed task was observed in patients with MCI. The FRT task should further be explored for its role as a marker for cognitive decline in elderly individuals, particularly in those with MCI.

Pairing of a gustatory CS and the visceral US induced by lithium chloride (LiCl) results in reduction of consumption of CS solution. This reduction is termed conditioned taste aversion (CTA). Pre-exposure to CS alone prior to the conditioning disrupts the conditioning (latent inhibition) and so is pre-exposure to US. The US pre-exposure effect is hypothesized to be due to tolerance, habituation, or the associative blocking effect. We studied the dose effect of US pre-exposure on CTA. In 3 experiments, rats were exposed to 10 doses of LiCl before the CTA procedure that consisted of ingesting a saccharin solution (0.1%) followed by injection of a constant dose of LiCl (7.632mg/rat). If the pre-exposure reduced the associability of the US, the CTA should be less. Exp. 1: Pre-exposure to 4 or 8 ml/kg of 0.15M LiCl, 1, 2 or 4 days prior to CTA did not have effect. Exp. 2: Pre-exposure to 0.5, 1, 2, 16, 32 ml/kg 1-day prior disrupted CTA. Exp. 3: Pre-exposure to 1, 16, 20, 32, 40 ml/kg 2-days prior disrupted CTA. Summary: (a) The pre-exposure effect was the same whether the pre-exposure occurred 1 or 2 days prior to conditioning. (b) A clear dose-effect relationship existed. (c) The relation was not monotonic. (d) The lowest preexposure dose, 0.5ml/kg of 0.15M LiCl, not strong enough to induce CTA by itself, was effective. (e) Upon repeated pairing of CS and US, CTA became more pronounced. The results do not support the hypotheses mentioned earlier.

Conditioned taste aversion (CTA) is traditionally viewed as an instance of pavlovian conditioning. This interpretation rests on the lack of an instrumental contingency between the tastant and the gastric malaise in a standard procedure of CTA. To investigate a role for instrumental punishment in CTA, we present 2 tastants sequentially ("sucrose then NaCl" or "NaCl then sucrose") in a daily alternating and counterbalanced order to rats with an explicit positive contingency between the dosage of the lithium chloride (LiCl) administered and the amount of 1 tastant drunk on that trial. In the beginning of experiment, rats suppressed their intake of both tastants. With the increase of conditioning trials, rats gradually learned to resume the intake of noncontingent solution while selectively suppressing the intake of LiCl-contingent solution. This selective suppression in CTA is the first report indicating that rats are sensitive to the subtle cues related to the covariations between the magnitude of stimulus and the magnitude of responses in a punishment paradigm involving a long delay between the gustatory stimulus of tastant ingestion and the aversive effect of LiCl injection.

While it is known that the brain perceives color and motion asynchronously, the specific locations in which the brain binds signals remain unknown. This study distinguishes subjective perception of the capability to bind features and the objective accuracy in feature binding. The stimuli were the same for individual subjects, consisting of random dots (red and green, or yellow and blue) moving either vertically or horizontally. Subjects responded to questions regarding the color or the direction of motion of the dots (objective judgment) and rated their capability in performing the task (subjective judgment). The imaging results of contrasting subjective judgment showed that the activation of the anterior rostral cingulate cortex (rACC) and inferior frontal gyrus (Brodmann area [BA] 45/47) during incapable-of-binding responses, compared with the capable-of-binding responses. It is suggested that the rACC is for uncertainty of subjective judgment and BA 45/47 is for the increased burden on working memory. In contrast, there was no imaging results of contrasting the correct and incorrect responses (i.e., objective judgment), and neither was there for the interaction between subjective and objective judgment. The results of conservative conjunction analysis indicated common and shared brain areas for the 2 distinctive binding situations (the correct and capable-of-binding vs the incorrect and incapable-of-binding), including increased activity in the intraparietal lobe (IPL) and the junction areas of the posterior rostral ACC (dACC) and the prefrontal areas, but decreased activity in the medial portion of the IPL, suggesting that feature binding requires maintaining attention. These results clearly isolated subjective judgment from objective judgment and support the view that maintaining attention is involved in feature binding of color and motion.

Extinguishing fear conditioning and preventing the return of fear are the goal in the treatment of anxiety disorders. However, the neural substrates that mediate fear conditioning, extinction, and spontaneous recovery (i.e., the return of fear) remain uncertain. We utilized the aversive passive avoidance learning paradigm and Fos-like immunoreactivity to elucidate this issue. Exception for naïve rats that did not receive any treatment served as the control group, the other rats were subjected to three sessions of context/footshock (0.5 mA, 2s) pairings followed by 12 extinction sessions (context-no footshock). After the last extinction test, these rats were assigned to one of three groups reflecting the number of resting days before the test session (context-no footshock): Day 8, Day 9, and Day 10 groups. Only the Day 10 group exhibited spontaneous recovery during the test session. Fos-like immunoreactivity associated with fear conditioning was seen in the amygdala and cingulate cortex area 1 (Cg1). The extinction of fear was seen to be related to Cg1, cingulate cortex area 2 (Cg2), piriform cortex (Pir), and entorhinal cortex (Ect). Spontaneous recovery was seen to be related to amygdala, Pir, and Ect. The present findings indicate that the brain substrates of fear acquisition, extinction and spontaneous recovery have different ensembles of brain activations. These differences suggest that different brain targets may be considered for fear extinction and for avoiding the return of fear in anxiety disorders.

The neural substrates of the unconditioned and conditioned components of amphetamine (AMPH)-induced behavioral sensitization remain unknown. The present study examines the brain activation of rats in response to an AMPH challenge with augmented locomotion in groups receiving chronic AMPH under chloral hydrate anesthetization (i.e., the ‘zero context’) or when tested in the ‘same context’ as a chronic treatment, or when tested in a ‘different context’. The neural activations of the three groups reveal fairly consistent patterns: (a) The substantia nigra is activated in the same context condition and the pure AMPH effect (i.e., the zero context with the unconditioned component), but not in the switch context condition. (b) The ventral pallidum showed Fos expression in the switch context and the same context, but not in the zero context condition. (c) The other nuclei, including the medial prefrontal cortex, nucleus accumbens, caudate putamen, medial thalamus, hippocampus, amygdala, and ventral tegmental area, are activated in all contextual conditions and the pure AMPH effect (the zero context). The context exerts definable effects on the mesocorticolimbic dopamine system on AMPH-induced behavioral sensitization. (d) The ventral pallidum and the substantia nigra activations dissociate the unconditioned component from the conditioned component in behavioral sensitization. Further studies are needed to determine how these two nuclei mediate the effect in terms of primary and conditioned rewards.

The Chinese Facial Emotion Recognition Database (CFERD), a computer-generated three-dimensional (3D) paradigm, was developed to measure the recognition of facial emotional expressions at different intensities. The stimuli consisted of 3D colour photographic images of six basic facial emotional expressions (happiness, sadness, disgust, fear, anger and surprise) and neutral faces of the Chinese. The purpose of the present study is to describe the development and validation of CFERD with nonclinical healthy participants (N=100; 50 men; age ranging between 18 and 50 years), and to generate normative data set. The results showed that the sensitivity index d' [d'=Z(hit rate)-Z(false alarm rate), where function Z(p), p∈[0,1]], for all emotions was 0.94. The emotion was more readily detected in happiness, and less easily detected in surprise and sadness. In general, this study replicated the previous findings on the recognition accuracy of emotional expression with the Westerner faces. However, our paradigm extends the previous work by including a wider sensitivity range to differentiate subtle perception of emotion intensities. The CFERD will be a useful tool for emotion recognition assessment in affective neurosciences research, especially for the Chinese and cross-cultural studies.

The relationship between declining performance, as measured by changes in reaction time, and declining cognitive function has not been critically studied. The aim of the present study was to investigate the association between reaction time during a task and cognitive ability in elderly Taiwanese individuals.Patients aged 65 years or older with mild cognitive impairment (MCI) (n = 33) and Alzheimer's disease (n = 26) were recruited from the neurology clinic of a regional hospital in southern Taiwan. In addition, 28 healthy controls aged 65 years or older were recruited from the community. The cognitive performance of the study participants was assessed using the Cognitive Abilities Screening Instrument (CASI). A computer-administered simple reaction time (SRT) task and a flanker reaction time (FRT) task were administered to assess participants' cognitive function. A non-parametric Kruskal-Wallis test was performed to compare CASI scores, SRT, and FRT among the three groups. anova was also used to compare CASI scores, inverse-transformed SRT, and inverse-transformed FRT among the three groups, with adjustment for age and years of education. Additionally, Pearson's partial correlation coefficients were used to assess the association of CASI scores with inverse-transformed SRT, and inverse-transformed FRT within each of the three groups.Significant differences in CASI scores, SRT, and FRT were found between the Alzheimer's disease group and the other two groups, either with or without adjustment for age or education. The reaction time of patients with Alzheimer's disease was significantly slower than the other two groups. Moreover, significant correlation between CASI and FRT was found in patients with MCI.Altered performance in a speed task was observed in patients with MCI. The FRT task should further be explored for its role as a marker for cognitive decline in elderly individuals, particularly in those with MCI.

Purpose Light therapy was only partially effective in treatment of depression when compared with summer's sunlight. The antidepressant effect of infrared irradiation was evaluated using an experimental animal model. Methods Seventeen mice were randomly assigned to the exposure group (n = 9) and the control group (n = 8). The mice in the exposure group received infrared irradiation for 60 min daily during the study period of 4 weeks. The two groups were given forced swim test once a week to evaluate depression with the measurement of the immobility time. Results We found that the exposure group showed a tendency of less immobility time by the end of the 3rd week when compared with the control group, and at the end of 4th week the difference reached a statistical significance (t15 = 2.873; p = 0.012). Conclusions The result indicates that the immobility time in forced swim test, the sign of depression, can be reduced after prolonged (4 weeks) exposure to infrared irradiation in the animal model. The result suggests that a continuous application of infrared irradiation has antidepressant effect.

This study assessed facial emotion recognition abilities in subjects with paranoid and non-paranoid schizophrenia (NPS) using signal detection theory. We explore the differential deficits in facial emotion recognition in 44 paranoid patients with schizophrenia (PS) and 30 non-paranoid patients with schizophrenia (NPS), compared to 80 healthy controls. We used morphed faces with different intensities of emotion and computed the sensitivity index ( d′ ) of each emotion. The results showed that performance differed between the schizophrenia and healthy controls groups in the recognition of both negative and positive affects. The PS group performed worse than the healthy controls group but better than the NPS group in overall performance. Performance differed between the NPS and healthy controls groups in the recognition of all basic emotions and neutral faces; between the PS and healthy controls groups in the recognition of angry faces; and between the PS and NPS groups in the recognition of happiness, anger, sadness, disgust, and neutral affects. The facial emotion recognition impairment in schizophrenia may reflect a generalized deficit rather than a negative-emotion specific deficit. The PS group performed worse than the control group, but better than the NPS group in facial expression recognition, with differential deficits between PS and NPS patients.

To characterize nocifensive behavior, a laser beam was applied to the hind footpad of nonanesthetized and unrestrained rats and the reaction pattern was analyzed. Fifty-four rats were divided into nine groups of six animals, and each group was given one of nine combinations of laser stimuli: intensity of 4, 8 or 12 W and duration of 10, 30, or 50 ms. A single pulse was applied to a 0.13 cm2 area of right or left footpad and the trial was repeated 20 times with 3 min between trials. The behavior was videotaped and reviewed for a period of 2 min following each stimulation. It seemed to consist of eight discrete responses, and each response was scored for whether it occurred and for its summed duration per trial. The component responses and the behavior as a whole were characterized by their sensitivity in terms of the level of energy required to attain 50% of the maximum response, and their linear or quadratic trends with increasing stimulus energy. The most sensitive index of pain stimulation was the composite score, followed by foot jumping, foot elevation, body movements, licking, and then foot movements. As stimulus energy increased, rats exhibited a greater number of different responses and a greater frequency of each component response. The results suggest that a pool of hierarchically organized responses in the nocifensive motor system are recruited partially or wholly by nociceptive stimuli of varying intensity.

Dopaminergic D1 and D2 antagonists decrease the intake of sweet solutions during sham feeding. Because the decreased intake of 10% sucrose produced by the D1 and D2 antagonists has been demonstrated to occur in the absence of significant deficits in the initiation of ingestion, or of its motor performance, we investigated the hypothesis that raclopride decreases intake by lowering the reinforcing potency of the orosensory stimulation provided by sucrose during sham feeding. Rats were adapted to ingest two differently flavored 10% sucrose solutions for 5 min in one-bottle tests. The flavored solution that rats preferred was paired with pretreatment with a dose of raclopride (400 micrograms/kg, IP, 15 min) that produced a mean decrease of intake of 55%. The other flavored 10% sucrose solution was paired with vehicle (0.15 M NaCl) injections. After three or six pairings with raclopride or vehicle injection, two two-bottle preference tests were given without raclopride pretreatment. Preference for the flavored 10% sucrose solution previously paired with raclopride decreased significantly in both tests. We interpret this decreased preference as evidence that raclopride decreased the reinforcing potency of flavored 10% sucrose during one-bottle tests. This is consistent with our hypothesis and with the more general hypothesis of Wise that central dopaminergic mechanisms mediate the reinforcing effect of food.

The neural substrates of the unconditioned and conditioned components of amphetamine (AMPH)-induced behavioral sensitization remain unknown. The present study examines the brain activation of rats in response to an AMPH challenge with augmented locomotion in groups receiving chronic AMPH under chloral hydrate anesthetization (i.e., the 'zero context') or when tested in the 'same context' as a chronic treatment, or when tested in a 'different context'. The neural activations of the three groups reveal fairly consistent patterns: (a) The substantia nigra is activated in the same context condition and the pure AMPH effect (i.e., the zero context with the unconditioned component), but not in the switch context condition. (b) The ventral pallidum showed Fos expression in the switch context and the same context, but not in the zero context condition. (c) The other nuclei, including the medial prefrontal cortex, nucleus accumbens, caudate putamen, medial thalamus, hippocampus, amygdala, and ventral tegmental area, are activated in all contextual conditions and the pure AMPH effect (the zero context). The context exerts definable effects on the mesocorticolimbic dopamine system on AMPH-induced behavioral sensitization. (d) The ventral pallidum and the substantia nigra activations dissociate the unconditioned component from the conditioned component in behavioral sensitization. Further studies are needed to determine how these two nuclei mediate the effect in terms of primary and conditioned rewards.

The present study used the preproenkephalin knockout (ppENK) mice to test whether the endogenous enkephalins deficit could facilitate the anxiety- and depressive-like symptoms of posttraumatic stress disorder (PTSD). On Day 1, sixteen wildtype (WT) and sixteen ppENK male mice were given a 3 mA or no footshock treatment for 10 seconds in the footshock apparatus, respectively. On Days 2, 7, and 13, all mice were given situational reminders for 1 min per trial, and the freezing response was assessed. On Day 14, all mice were tested in the open field test, elevated plus maze, light/dark avoidance test, and forced swim test. Two hours after the last test, brain tissues were stained to examine c-fos expression in specific brain areas. The present results showed that the conditioned freezing response was significant for different genotypes (ppENK vs WT). The conditioned freezing effect of the ppENK mice was stronger than those of the WT mice. On Day 14, the ppENK mice showed more anxiety- and depressive-like responses than WT mice. The magnitude of Fos immunolabeling was also significantly greater in the primary motor cortex, bed nucleus of the stria terminalis-lateral division, bed nucleus of the stria terminalis-supracapsular division, paraventricular hypothalamic nucleus-lateral magnocellular part, central nucleus of the amygdala, and basolateral nucleus of the amygdala in ppENK mice compared with WT mice. In summary, animals with an endogenous deficit in enkephalins might be more sensitive to PTSD-like aversive stimuli and elicit stronger anxiety and depressive PTSD symptoms, suggesting an oversensitivity hypothesis of enkephalin deficit-induced PTSD.

We studied whether a cascade of different phases of ingestive behavior were governed by different doses of the dopamine D2 receptor system. A wide spectrum of doses (0, 0.025, 0.05, 0.1, 0.2, and 0.4 mg/kg) of a D2 receptor antagonist, haloperidol, were administered to 6 groups of water-deprived rats. 45 min following administration of the drug a 15 min water intake session was allowed to assess the effect on (a) locomotion, (b) appetitive response and (c) consummatory responses. The procedure was repeated for 5 days. Results: The doses of 0.025 to 0.1 mg/kg had no effects on any measured behavior compared with the control group. The 0.2 mg/kg dose induced catalepsy during sessions 3 and 5 and impaired consummatory (decreased lick numbers and intake volume) behaviors during sessions 1–5. The 0.4 mg/kg dose affected appetitive behavior (increased latency to contact the water tube) during session 2 and consummatory behavior during all five water sessions. The 0.2 mg/kg dose appeared to dissociate appetitive and consummatory behavior, and the 0.4 mg/kg dose locomotor activity and motivational behavior (including consummatory and appetitive responses). These results, that the three elements of ingestive behavior (locomotion, appetitive responses, and consummatory behavior) have different sensitivity to haloperidol, suggest that separable D2 mechanisms are involved in governing the ingestive behavior.

The paradoxical phenomenon of co-existing physically aversive and psychologically rewarding effects of drugs is a crucial issue for drug addiction. The present study employed a new experimental paradigm to test whether the rewarding and aversive properties of amphetamine (AMPH) can exist simultaneously. Rats were given a 15 min period of exposure to saccharin injected with 0.15 M NaCl or 1.5 mg/kg AMPH and then were confined to one compartment of a test box for 30 min. After three paired and unpaired cycles, the aversive and rewarding effects were assessed. A reduction in consumption of the paired flavored solution provided evidence of avoidance while preference for the AMPH injection context provided evidence of rewarding effects. The present findings demonstrate that the development of AMPH-induced rewarding and aversive effects depends on the particular behavioral conditions and support both the task-dependent drug effects hypothesis and the reward comparison hypothesis. The formation of associations with stimuli that comes before (pre) vs. after (post) the unconditioned stimulus and the role of the dopaminergic system in such associations are discussed.

This study reexamined Grigson's reward comparison hypothesis (1997), which claimed to have resolved the paradox of addictive, rewarding drugs manifesting an aversive effect in the conditioned taste aversion (CTA) paradigm. Here, the authors compared the conditioned suppression effects of lithium chloride (LiCI) and amphetamine in a series of three experiments. In Experiment 1, the concentrations of saccharin solution (conditioned stimulus [CS]) and the doses of amphetamine or LiCI (unconditioned stimulus [US]) were manipulated. In Experiment 2, the effects of employing backward versus forward pairings of the CS and US were compared. Finally, in Experiment 3, the additivity of amphetamine's reward property and LiCl's aversive property was examined. The results of these experiments, respectively, indicated that: (1) manipulating saccharin solution concentrations does not distinguish the suppression effect caused by rewarding or aversive effects when amphetamine or LiCI served as the US; (2) both backward and forward pairings produced suppression of saccharin solution intake regardless of whether amphetamine or LiCI was used as the US; and (3) combining amphetamine and LiCI did not diminish the suppression effect, as would be expected if they had opposing mechanisms for the effects; instead, an additive effect occurred. Taken together, these results suggest that the drug of abuse amphetamine and the emetic drug LiCI both possess aversive properties in the CTA paradigm. No rewarding effects of amphetamine were detected in our experimental data. In all, our results do not support the Grigson's reward comparison hypothesis (1997) and a new "task-dependent drug effects hypothesis" is proposed.

The aim of this study was to identify the neural substrates of online gaming addiction through evaluation of the brain areas associated with the cue-induced gaming urge. Ten participants with online gaming addiction and 10 control subjects without online gaming addiction were tested. They were presented with gaming pictures and the paired mosaic pictures while undergoing functional magnetic resonance imaging (fMRI) scanning. The contrast in blood-oxygen-level dependent (BOLD) signals when viewing gaming pictures and when viewing mosaic pictures was calculated with the SPM2 software to evaluate the brain activations. Right orbitofrontal cortex, right nucleus accumbens, bilateral anterior cingulate and medial frontal cortex, right dorsolateral prefrontal cortex, and right caudate nucleus were activated in the addicted group in contrast to the control group. The activation of the region-of-interest (ROI) defined by the above brain areas was positively correlated with self-reported gaming urge and recalling of gaming experience provoked by the WOW pictures. The results demonstrate that the neural substrate of cue-induced gaming urge/craving in online gaming addiction is similar to that of the cue-induced craving in substance dependence. The above-mentioned brain regions have been reported to contribute to the craving in substance dependence, and here we show that the same areas were involved in online gaming urge/craving. Thus, the results suggest that the gaming urge/craving in online gaming addiction and craving in substance dependence might share the same neurobiological mechanism.

This study aimed to identify risk factors involved in Internet addiction. A total of 216 college students (132 males and 84 females) were given the following: (a) the diagnostic interview for Internet addiction, (b) the Iowa gambling test for decision-making deficits, (c) the Balloon Analog Risk Test (BART) to assess risk-taking tendencies, and (d) the Tridimensional Personality Questionnaire (TPQ) for personality characteristics. The results revealed the following: (a) 49% of males and 17% of females were addicted, (b) the addicted students tended to select more advantageous cards in the last 40 cards of the Iowa test, indicating better decision making, (c) no difference was found for the BART, indicating that addicted subjects were not more likely to engage in risk-taking behaviors and (d) TPQ scores showed lower reward dependence (RD) and higher novelty seeking (NS) for the addicts. Their higher performance on the Iowa gambling test differentiates the Internet addiction group from the substance use and pathologic gambling groups that have been shown to be deficient in decision making on the Iowa test. Thus, students that fit these characteristics should be closely monitored to prevent Internet addiction.

We tested the hypothesis that educational level influences regional cerebral blood flow (rCBF) in Alzheimer's disease (AD) patients.The severity of AD was measured with the Cognitive Ability Screening Instrument (age and education adjusted). rCBF was assessed using (99m)Tc-hexamethylpropyleneamine oxime brain SPECT; differences in rCBF between groups with different educational levels were determined using statistical parametric mapping (SPM).In matched low-education (or =6 y; n = 29) and high-education (6 y; n = 29) groups, SPM revealed 2 statistically significant clusters of voxels with higher rCBF in the high-education group: one in the left lateral inferior, middle, and superior temporal gyrus; another in the left medial temporal area to the left inferior frontal gyrus.We provide biologic evidence that education may lead to relatively higher rCBF in specific areas in AD patients, which may explain the effects of education on clinical manifestations of AD.

Rats, pretreated with amphetamine (AMPH, 1 mg/kg) or saline for 2 weeks, were challenged with AMPH (0.5 mg/kg) or saline following 1 week of abstinence, and locomotion was measured. In Experiments 1 and 2, the pretreatment occurred in various contexts (home cage, novel box, test box). Sensitization was observed only when pretreatment context and test context were the same; a context switch abolished sensitization. When rats anesthetized with chloral hydrate were pretreated with AMPH, sensitization was completely dependent on the pretreatment, but independent of context. This "zero context" condition isolated the basal level of excitation attributable to unconditioned neural change to determine the role of contextual input to be a modulator that enhances or inhibits sensitization.

Estrogenic modulation of body weight in female rats is usually thought to result indirectly from estrogenic modulation of food intake. The data presented here suggest, however, that estrogens influence body weight by at least two mechanisms, one of which is independent of changes in food intake. When female rats were ovariectomized (Ovx) and food intake was limited to preoperative levels, the Ovx animals nonetheless gained large amounts of body weight. Although Ovx rats gained more weight than controls on the same amount of food, during 33 hr of food deprivation Ovx and control animals lost body weight at the same rate, which indicates that the prefasting metabolic rates of the two groups were generally similar. Examination of recovery from food deprivation suggested that the rate of weight gain after Ovx was very gradual. During the first 40 days after surgery, the ano-nasal lengths of Ovx rats increased twice as fast as the ano-nasal lengths of the intact rats, which suggests a mechanism for the gradual increase in body weight induced by Ovx. The body weights of intact rats followed a regular 4-day cycle during ad lib feeding but when the estrus-associated decrease in food intake was prevented the cyclic body weight changes were dramatically altered. Thus estrogens appear to regulate body weight by at least two mechanisms: modulation of food intake (cycling females) and modulation of ano-nasal growth or other metabolic processes (Ovx females).

The effect of cholecystokinin tetrapeptide (CCK-4) was studied in an open field situation. CCK-4 increased locomotion and rearing and the effect was enhanced by proglumide, a selective antagonist of CCK-8. This is in sharp contrast to our earlier findings that CCK-8 decreased the open-field behavior and that proglumide completely blocked the effect. Thus, the effects of CCK-4 and CCK-8 appear to be opposite to each other in that one is excitatory and the other inhibitory to open-field responses.

The effects of intracerebroventricular injection of mu (morphine), kappa (dynorphin-(1-13), ethylketocyclazocine, and U50,488H), and delta ([D-Pen2, D-Pen5]enkephalin) opioid agonists on water intake of 14 hr water deprived rats was studied. All agonists caused a dose related decrease in time spent drinking, with a rank order potency of dynorphin-(1-13) greater than morphine greater than ethylketocyclazocine greater than [D-Pen2, D-Pen5]enkephalin = U50, 488H. With the exception of morphine, all of the compounds increased the latency to begin drinking, but only at the highest doses tested. The rank order potency for this endpoint was dynorphin-(1-13) = ethylketocyclazocine greater than [D-Pen2, D-Pen5]enkephalin greater than U50, 488H. The potent inhibition of drinking following centrally-given dynorphin-(1-13), at doses that did not affect the latency to begin drinking, supports a role for endogenous dynorphin in the homeostatic control of water balance. This function may not be primarily mediated through activation of a kappa opioid receptor since dynorphin-(1-13) was 80-230 times more potent than the selective kappa agonist, U50,488H or ethylketocyclazocine.

Self-mutilation in humans occasionally accompanies physiological disorders such as the deLange syndrome. If pemoline-induced self-biting is behaviorally similar to self-mutilation in the deLange syndrome, similar neurochemical mechanisms may be involved in both. Oral administration of 140 and 220 mg/kg pemoline reliably induced persistent self-biting in rats. This behavior was indistinguishable from stereotyped grooming and its most common target was the medial digits of the foreleg. Pemoline-induced self-biting was accompanied by hyperactivity, stereotyped behavior, abnormal social behavior, abnormal sensorimotor behavior, and unresponsiveness or avoidance of moderate levels of sensory stimuli. Several of these behaviors have also been reported in deLange patients.

An open field apparatus was used to assess the effect of proglumide, a selective antagonist of cholecystokinin octapeptide (CCK-8), to block the behavioral effect of CCK-8 in rats. Intracerebroventricular (ICV) injection of CCK-8 (0.5 to 2 micrograms) was effective in suppressing general exploratory activities and this effect was blocked by proglumide at doses of 2 to 5 micrograms administered ICV or 1 mg/kg administered subcutaneously. The effect of peripherally administered CCK-8 (10 micrograms/kg) was blocked by peripherally administered proglumide at a dose of 2 mg/kg but not by centrally administered proglumide at a dose of 5 micrograms/rat. The behavioral effect of CCK-8 was thus clearly blocked by proglumide.

The analgesic effects of intracerebroventricular injections of Met-enkephalin and five of its analogs in a dose of 10 micrograms each were quantified with a hot plate test in rats. Two analogs showed analgesic effect. [D-Ala2, Met5]-enkephalin had a weak and short-lasting analgesic effect. [D-Ala2, Met5]-enkephalinamide (DALA) had a striking and long-lasting analgesic effect. However, sulfation of tyrosine residue totally abolished the analgesic action of DALA. The analgesic effect of DALA was not affected by preinjection of its sulfated analog.

The C-terminal octapeptide of cholecystokinin (CCK) was injected into water-deprived rats to observe the effect on water and milk intake. The doses used were 0, 20, and 40 Ivy dog units/kg. The data indicated that milk intake was suppressed in a dose-related fashion within 2–4 min of injection but water intake was not suppressed. This stiety hormone is thus specific to food intake.

A low dose intracerebroventricular injection of thyrotropin releasing hormone (TRH, 100 ng) changed many behavioral responses in the rat. TRH increased locomotion, scratching, body shaking, piloerection, and rearing, but decreased sniffing, and resting. Ablation of frontal neocortex further enhanced the TRH effects on locomotion and resting. A dose effect of TRH (0, 5, 10, 50, 100 ng) to increase general activity was established and the effect was further enhanced by decortication. In our test situations decortication had no effect by itself. Since the TRH effects became much more pronounced without the frontal neocortex it appears that the cortex exerts a powerful inhibitory effect to moderate the TRH effects. The TRH effect does not depend upon the frontal cortex, actually a cortical function is to dampen the TRH effects on various behavioral responses.

Cholecystokinin (CCK) is a putative short-term satiety hormone which may regulate meal size and the intermeal interval. A series of criteria are proposed to determine whether CCK can be regarded as a short-term satiety hormone. The available data indicate that the CCK-induced inhibition of food intake may not be chemically specific (to CCK) but is behaviorally specific (to ingestive responses). The physiological nature of the necessary doses is unclear. The effects of CCK seem to simulate natural satiety, and these effects appear to be consistent across wide ranges of nutritional deficit. The mechanism of the effect may involve the feeding-associated areas of the brain. The effect has been shown in rats and monkeys, but data from humans have been inconsistent. CCK appears to be a promising factor which may participate in natural satiety along with many other factors.

The ability of cholecystokinin (CCK), a putative intestinal satiety hormone, to delay the usual onset of a meal was investigated by administering its pure, synthetic octapeptide from during the intermeal interval. In the first experiment, a single intraperitoneal injection of CCK was given during the short interval that typically follows a small spontaneous meal in undeprived rats. In the second experiment, continuous intravenous infusions of CCK were given throughout the long intermeal interval that follows the relatively large first meal eaten by mildly (6 hr) food-deprived rats. The results were that CCK prolonged the intermeal interval in both situations by considerably delaying the start of the next meal. This effect was dose dependent, and did not appear to be related to any alteration of sensorimotor behavior. In a third experiment, CCK was administered prior to the onset of the very first meal in mildly food-deprived rats. The results were that eating was initiated without delay and without any change in rate. Only the size of the meal was decreased, due to a shorter the meal despite the action of CCK. When the meal was to external cues may have stimulated the rats to initiate the meal despite the action of CCK. When the meal was partially completed, the CCK satiety effects then became measurable. Taken together, the three experiments suggest that CCK can affect meal initiation but is effective only when other short-term satiety mechanisms are partially operative. The implications for the potential clinical use of CCK in weight control were briefly discussed.

The effective intravenous dose of angiotensin II for the induction of drinking in the rat has been reduced to a physiologically reasonable level of approximately 10 ng/min/rat or 25 ng/min/kg. It can be as low as 4 ng/min/rat when the natural state of thirst is more closely simulated with concurrent cellular dehydration. These doses are not different from those employed intravenously in the intact mammal to produce the hormone's pressor response. In addition: (i) the drinking produced by the hormone occurs sooner and more reliably and is greater in volume when the hormone is combined with mild cellular dehydration, and (ii) the drinking is blocked by a specific competitive inhibitor of angiotensin II, but (iii) is not affected by diurnal cycle. The evidence supports the suggestion that angiotensin II is a normal participant in drinking provoked by hypovolemia.

Licking patterns and molarity preferences, elicited by two sets of sucrose solutions (0.0 to 1.75 M and 1.0 to 3.0 M), were measured in six young and six aged squirrel monkeys. Sucrose preference thresholds were determined for each age group using sucrose concentrations from 0.025 to 0.1 M. Age was unrelated to sucrose preference thresholds. Consummatory activity of all monkeys increased monotonically as sucrose concentrations increased from 0.0 to 1.0 M. Aged, but not young, monkeys continued to increase consumption until sucrose concentrations exceeded 1.5 M. All monkeys increased consumption by increasing number of licks, number of licking bursts and total time spent licking. Unlike young monkeys, aged monkeys displayed high within animal variability of tongue contact times, exponentially decreasing rates of licking at high molarities, constant consumption efficiency decrements, and consistent negative correlations between tongue contact and following tongue off times.

Rats were deprived of water for 24 h and given 8 ml of water, .9% saline, 1.8% saline, or 4 ml of water via stomach-tubing or via normal drinking. Immediately following administration of liquid, subjects were given either food or water for 30 min. The results showed that: (a) orally ingested liquids were more effective than stomach-tubed liquids in inhibiting drinking and in potentiating feeding; (b) a higher concentrated NaCl solution was less effective in inhibiting water intake and potentiating food intake; (c) a greater amount of water was more inhibitory to subsequent water intake but more potentiating to food intake within the range tested. Thus the ingestional, amount, and osmolality variables related to liquid intake reciprocally influenced feeding and drinking.

Rats were food-rationed (15 g/day) and trained to bar-press for food. In Experiment 1, the animals were injected with cholecystokinin octapeptide (CCK, 2 micrograms/day), bombesin (BBS, 12 micrograms/kg), normal saline, or prefed with 20 Noyes 45 mg pellets. The animals were then tested for one hour for bar-pressing responses with food reward. In Experiment 2, the animals were similarly trained, treated, and tested for bar-pressing responses without food reward. The results showed that BBS and prefeeding decreased bar-pressing, rewarded or non-rewarded, but the CCK effect was greatly decreased when food was withheld. It appeared that the CCK effect was more dependent upon the presence of food than the BBS or prefeeding effects. The results were discussed in terms of involvement of the food and reward-related oropharyngeal stimuli for the CCK effect and the drive-related stimuli for the BBS and prefeeding effects.

Hippocampus damaged, neodecorticate, and normal control rats were tested in a Maier three table situation. One goal was baited with food, the other with water. The animals were food or water deprived on alternate days and trained to run to the appropriate goal. After reaching criterion, reversal learning was begun. The results showed that neodecorticate and normal rats switched responses to obtain appropriate rewards but hippocampal rats were deficient in learning this. The hippocampal group had high total errors and a strikingly high proportion of such errors were committed consecutively. Upon reversal, both hippocampal and neodecorticate rats initially had high error scores. On the seventh day of reversal learning the hippocampal group still had a mean of 3 errors while the others had 1 error. The results were discussed in terms of perseverative tendencies and a lack of attention to relatively minor but crucial stimuli.

Four groups of rats were deprived of water for 24 hr and first allowed to drink 6 ml either of water, 0.25% saccharin solution, 3% glucose solution, or a mixture of 0.25% saccharin 3% glucose solution, subsequently they were given a 3% glucose solution for 20 min. The glucose solution was given either immediately or 30 min after the intake of 6 ml of the 4 experimental liquids. With immediate presentation the glucose intake was lowest following ingestion of the saccharin-glucose solution, next lowest, following ingestion of the saccharin solution and third lowest, following the glucose solution. The glucose intake was highest following water ingestion. However, with the 30-min delay period the differences dissipated. Saccharin and glucose solutions appear to generate a short-term satiety effect which inhibits subsequent intake of glucose solution.

Rats were given either 0, 3, 6, 9 g, or unlimited amounts of food accompanied by either water, 0.45 per cent NaCl, 0.9 per cent NaCl, 0.4 per cent saccharin, 4.6 per cent sucrose, or 9.3 per cent sucrose solutions for 24 hr; liquid or food intake for this period was recorded. The results indicate that (a) as food ration is decreased rats drink less water or saline solution but more sucrose or saccharin solutions, and (b) with ad lib food, food intake is reduced when accompanied by the liquids with calories but food intake is constant with liquids having no calories regardless of the osmotic or taste differences.