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Piracetam is an AMPAkine drug that may have a range of different mechanisms at the cellular level, and which has been shown to facilitate memory, amongst its other effects. This series of experiments demonstrated that a 10mg/kg dose of piracetam facilitated memory consolidation in the day-old chick when injected from immediately until 120min after weak training (i.e. using a 20% v/v concentration of methyl anthranilate) with the passive avoidance learning task. Administration of piracetam immediately after training led to memory facilitation which lasted for up to 24h following training. This dose of the AMPAkine was not shown to facilitate memory reconsolidation. These findings support the contention that application of the AMPAkine piracetam facilitates memory using a weak training task, and extend the range of actions previously noted with NMDA-related agents to those which also facilitate the AMPA receptor., (Copyright © 2012 Elsevier Inc. All rights reserved.)

This series of experiments investigated the role of protein translation and RNA synthesis on consolidation and reconsolidation of passive avoidance learning (PAL) in day-old chicks. Although it is well established that protein translation is required after a reminder, there are conflicting reports in the literature concerning the requirement for RNA synthesis at this time. Day-old male New HampshirexWhite Leghorn chicks were trained on a single trial passive avoidance task. The results confirmed the requirement for protein translation during reconsolidation with memory deficits induced by anisomycin (ANI) (10mg/kg) detected at 60min post-reminder. It was also established that RNA synthesis was required for consolidation of PAL through inhibition by 5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) (0.075microg/kg), administered at or after training. The same dose of DRB was also found to inhibit memory post-reactivation. However injections were required before the reminder trial and memory deficits were evident by 60min, consistent with that found for ANI post-reminder. As with ANI, the DRB-induced memory deficit post-reminder was also transient, and resolved by 24h post-reminder. For both reconsolidation drug studies, the memory deficit was wholly dependent on the memory being reactivated by a reminder-trial. The study highlights an important role for RNA synthesis following memory reactivation.

There is an increasing evidence that long-term alcohol intake can promote damage to most of the body's major organs. However, regular consumption of a small-moderate amount of alcohol is often recommended as being beneficial to health and of concern is that the effect of ingesting commercially available alcohol products on steroid hormone synthesis under variable nutritional conditions has not been thoroughly investigated. Many individuals consume alcohol alone prior to a meal and the aim of the present study was to assess the effect of consuming a small-moderate amount of commercially available alcohol on the level of salivary cortisol and salivary dehydroepiandrosterone sulfate (DHEAS) before and after a meal. A total of 24 males aged 19-22 years participated in the current investigation. The experimental procedure required participants to fast for 6 h before being asked to ingest either 40 g alcohol in the form of red wine (n=8), low alcohol and high beer (n=8), white wine (n=8) or the equivalent amount of placebo over a 135-min period before consuming food for 45-min. The level of blood alcohol, salivary cortisol and salivary DHEAS was assessed upon arrival and then at regular 45-min intervals during the 180-min experimental period. The results showed that the consumption of alcohol and placebo can significantly lower the level of salivary cortisol. However, the effect of consuming a small-moderate amount of commercially available alcohol on the level of salivary DHEAS was dependent on the nutritional content of the beverage with red wine promoting no change, white wine promoting a significant decrease, and beer having a variable effect on salivary DHEAS concentration when compared to placebo. It was concluded that the effect of commercially available alcohol on the HPA axis is not the same for all alcohol products and both the nutritional status of participants and the nutritional content of the alcoholic beverage being administered should be taken into consideration when investigating the effect of alcohol on the HPA axis.

This series of studies examined the effect of the PDE4 inhibitors rolipram and YM976 on the recall of the passive avoidance learning (PAL) task in the day old chick, with a particular focus on the role of D1 receptor in activating this pathway. The results indicated that 2.0 mg/kg rolipram administered 5 min before or immediately, 5, 15 or 30 min following training and 0.025 mg/kg YM976 administered 15 min before or immediately, 5, or 15 min following training facilitated recall of the weak form of the task (i.e. using 20% v/v methyl anthranilate (MeA) as the aversant) at 180 min following training. In each case the effect emerged from 60 min following the training, and was still observable from 180 min to 24 h after training. In addition, whilst administration of 0.5 mg/kg SCH23390, a D1 receptor antagonist, 10 min prior to training disrupted recall for the strong form of the task, co-administration of 2.0 mg/kg rolipram but not 0.025 mg/kg YM976 5 min prior to training prevented this disruption occurring. The results suggest a role for D1 receptor activation in the processes underlying the facilitation of memory by rolipram.

Cyclin-dependent kinase 5 (CDK-5) is reported to phosphorylate the NMDA receptor prior to the induction of long-term potentiation (LTP), among its many other effects. Application of CDK-5 inhibitors disrupts LTP and results in impaired task acquisition in behaving animals. In this study, we investigated the effect of exogenously applied roscovitine, a potent CDK-5 inhibitor, on consolidation and reconsolidation processes in day-old male chicks. New Hampshire x White leghorn cockerels were trained using a modified version of the passive avoidance learning task. Intracranial injections of roscovitine (2.5 microM) administered immediately after training induced a memory deficit that evolved from 5-minute post-training and persisted until at least 24 h following training. Injections of roscovitine (2.75 microM) administered immediately after the reminder trial induced a memory deficit observed by 30-minute post-reminder which had resolved by 24 h following the reminder. The comparison between consolidation and reconsolidation demonstrates differences both in the time of the onset of the memory deficit as well as in the permanence of this deficit. The results suggest an important, although different role for CDK-5 in consolidation and reconsolidation processes following passive avoidance learning.

This series of studies used a weakly trained (20% methyl anthranilate) version of the passive avoidance learning task in the 1-day-old chick to investigate memory facilitation effects by diphenylhydantoin (DPH). The results indicated that the pairing of the weak training experience with DPH results in facilitation of memory that can be observed from 40 min following training with the weak training experience. The results from a biochemical experiment indicated that DPH facilitates the activity of Na(+)/K(+)-ATPase at the majority of times sampled in a large percentage of the sections of the chick brain. The most marked level of elevation in the activity of the enzyme was observed at the 20-min time point following weak training in the section of the chick brain, which contained several memory relevant neuroanatomical loci. This represents a 68% increase in the activity of the enzyme in those areas considered to be crucial to the processing of memory in the paradigm at a time predicted by previous investigation to be crucial in the development of the intermediate-term memory stage of memory. The results of this series of studies support the notion that Na(+)/K(+)-ATPase plays an important role in memory processing following passive avoidance training in the 1-day-old chick.

The experiments reported in this series of studies demonstrate that thiamine deficiency, induced pharmacologically by oxythiamine (OT) coupled with the acute administration of ethanol can adversely affect memory processing in the young chick. The interaction between the avitaminosis and ethanol neurotoxicity exerted its effects through the inhibition of the development of the intermediate (ITM) stage of memory (i.e., following 10 min after training), consequently affecting development of the long-term stage of memory and leaving the short-term memory stage intact. The amnesic effect of OT-induced thiamine deficiency and exposure to alcohol was ameliorated by the administration of phenytoin [diphenylhydantoin (DPH)] immediately following the training experience. As the ITM stage of memory has been suggested to rely on the activities of Na(+)/K(+) ATPase, and as DPH is a facilitator of Na(+)/K(+) ATPase activity amongst its other actions, it may be that the combined effect of OT and ethanol exposure is by interfering with Na(+)/K(+) ATPase activity, thus undermining the expression and maintenance of the memory in the period from 10 min following aversant training.

The nutritional status of the individual at the time of alcohol consumption may mediate the rate of alcohol absorption and metabolism, thus influencing the systemic effect of alcohol on the body. The aim in the present investigation was to assess the effect of moderate white wine consumption on the hypothalamic-pituitary-adrenal (HPA) axis under variable nutritional conditions. Seven males aged between 19 and 22 years participated in all aspects of the current investigation. The experimental procedure for the fasting trial required participants to ingest either 4 standard units of alcohol (40 g) or the equivalent amount of placebo over a 135-min period before consuming food for 45 min. Alternatively, in the feeding trial, food was consumed for 45 min prior to participants ingesting either 4 standard units of alcohol (40 g) or the equivalent amount of placebo over a 135-min period. Blood alcohol, salivary cortisol, and salivary dehydroepiandrosterone sulfate (DHEAS) levels were assessed at 45-min intervals during the 180-min experimental periods. The results demonstrated a significant alcohol-induced decrease in salivary cortisol irrespective of nutritional status and a significant decrease in salivary DHEAS when alcohol is consumed alone under fasting conditions only. It was concluded that moderate white wine consumption may promote a transient alteration in the functioning of the HPA axis.

Recent evidence has demonstrated that immune activation can result in cognitive deficits due to the actions of the proinflammatory cytokines. These series of studies examined the effects of peripheral administration of lipopolysaccharide (LPS) on the memory processes of day-old chicks trained on a single-trial passive-avoidance task. LPS impaired performance in a dose- and time-dependent manner. Maximal impairment was produced by a dose of 2.5-mg/kg LPS administered 60 min prior to training. Retention tests revealed that deficits in memory processing appeared between 10 and 20 min posttraining. These results demonstrate an inhibitory effect of LPS on memory processing at the transition point from short-term memory to intermediate-term memory.

This series of experiments investigated the effect of the benzodiazepine diazepam on memory formation in day-old chicks trained on a single-trial, passive-avoidance task. The findings indicate that diazepam has a dose-specific and time-dependent effect on memory processes. A 0.125-mg/kg dose of diazepam administered immediately after training led to amnesia in these subjects only after 30 min following learning. Pretreatment with bicuculline and flumazenil were effective in ameliorating the memory deficits caused by diazepam, and consolidated memory function in saline-treated controls following strong and weak aversant training. These findings suggest that benzodiazepine effects on memory are mediated by their effects on arousal, possibly by the release of noradrenaline, which is critical to the establishment of long-term memory.

This series of studies revealed that a 2.5-mg dose of oxythiamine administered over 2 days yielded memory deficits from 10 min following passive avoidance learning. This result existed in association with slowing of righting reflex. Administration of thiamine reversed the memory deficit and the slowing of the righting reflex. A combination of oxythiamine and peripheral alcohol administration also resulted in memory deficits appearing from 10 min after training; however, in contrast to the effect of thiamine deficiency alone, the deficits induced by thiamine deficiency in association with acute administration of alcohol could not be reversed by thiamine resupplementation. The combination of alcohol and oxythiamine also slowed the righting reflex, but higher doses of thiamine also were unable to ameliorate the memory deficit caused by a combination of oxythiamine and alcohol; however, the slowing of righting reflex was reversed. The results suggest that preexistent thiamine deficiency may make the subject susceptible to the neurotoxicological effects of alcohol on memory function.

The results of this series of experiments with chicks trained on a single trial, passive avoidance task, demonstrate that methotrexate-induced folate deficiency, and excess levels of folate and B12 lead to amnesia in these subjects. The amnesia appears only after 50 min following learning, leaving the earlier processing stages of memory formation unaffected. The application of methotrexate resulted in disruption of righting reflex in a dose dependent manner, however the ataxia did not appear to be the cause of the memory deficit. The deficit in memory induced by methotrexate-induced folate deficiency could be ameliorated with methionine. These studies suggest that cellular processes involving folate metabolism may play an important role in the memory formation of the young chick and that the observed disruption of memory may well occur due to its affect on protein synthesis mediated by alterations in methionine metabolism.

Day-old chicks trained on a single-trial discriminated passive avoidance task using a concentrated taste aversant, methyl anthranilate, have been shown to exhibit three stages of memory processing; short-, intermediate-, and long-term memory. If the aversant is diluted to 20% v/v methyl anthranilate in absolute ethanol, only the short-term and some of the intermediate stage are observed. In this study we investigated the whole forebrain levels of noradrenaline in response to differing intensities of the training experience. The results show a profound difference in the level of whole forebrain NA at all training-sacrifice intervals for the trained as compared to the untrained controls, except at 15- and 20-minute posttraining, when a substantial reduction in the level of NA was achieved under all training conditions. Furthermore, subjects which received treatments which resulted in the emergence of behavioural evidence of long-term memory tended to have higher levels of whole-forebrain NA at 30 minutes after initial training. This is the time when we have postulated that triggering of protein synthesis associated with long-term memory formation takes place.

Day-old chicks trained on a single trial passive discrimination avoidance task using a concentrated chemical aversant, methyl anthranilate (MeA), have been shown to exhibit three stages of memory processing: short, intermediate and long term. A similar learning task with the aversant diluted to 20% in ethanol leads to short- and intermediate-term memory only, but not to long-term memory. The emergence of long-term memory has been shown to be associated with the production of a nonenergy-dependent phase of the intermediate memory stage. Subcutaneous administration of propranolol proved capable of inhibiting this nonenergy-dependent phase of memory under a number of training regimes: strongly reinforced training, and with weakly reinforced training presented twice or coupled with a selected dose of the stress-related hormone ACTH. This study supports the notion that there is a phase of memory that occurs prior to the protein synthesis-dependent phase of memory which is susceptible to interference by drugs affecting noradrenergic processes and which may be associated with the intensity of the training stimulus.

Day-old chicks trained on a single-trial passive discrimination avoidance task using a concentrated chemical aversant, methyl anthranilate (MeA), have been shown to exhibit three stages of memory processing; short-, intermediate- and long-term. A similar learning task with the aversant diluted to 20% in ethanol leads to short-and intermediate-term memory, but no long-term memory. Subcutaneous administration of selected doses of the stress-related hormones, noradrenaline, ACTH and vasopressin in close temporal proximity to the training trial, produced long-term memory in chicks trained on the weakly reinforced task, mimicking the outcome of strongly reinforced learning and of retraining with the weakly reinforced task reported previously. These effects are shown to be associated with the production of a nonenergy-dependent phase of the intermediate memory stage, postulated to be necessary for long-term memory consolidation.

Day-old chicks given a single weakly reinforced (20% v/v methyl anthranilate in absolute ethanol) passive avoidance learning trial showed no evidence of long-term memory. A second learning trial given at 15 minutes after initial resulted in consolidation of the learning experience into long-term memory. The retention function resulting from two learning trials is similar to that observed with a single strongly reinforced learning trial, and consists of the stages postulated by Gibbs and Ng. With a dilution of 10% methyl anthranilate in ethanol, four training trials were needed to yield unequivocal evidence of long-term memory consolidation.

Day-old chicks trained on a single-trail passive avoidance learning task, with varying concentrations of the aversive stimulus (methyl anthranilate), truncated retention functions for low concentrations. The retention function for a 20% v/v dilution of methyl anthranilate in absolute ethanol yielded high retention levels until approximately 40 to 45 minutes following learning. This retention function appears to consist of only the short-term and intermediate (phase A) memory stages of Gibbs and Ng's three-stage model of memory formation, with the short-term stage susceptible to inhibition by monosodium glutamate, and the intermediate stage by ouabain and dinitrophenol. The results suggest that processing of memory into the relatively permanent long-term stage may depend on the strength of the reinforcer in aversive learning.