Analysis of the avoidance learning deficit induced by the serotonin releasing compound p-chloroamphetamine

The effects of the serotonin-releasing compound p-chloroamphetamine (PCA, 2.5 mg/kg) on avoidance acquisition, retention and memory retrieval were examined in male Sprague-Dawley rats using a one-way active avoidance and a one-trial passive avoidance task. The drug was injected IP prior to training, following acquisition and prior to the retention test 24 hr after training using a state-dependent design. In the normal context situation pretraining administration of PCA markedly impaired active avoidance acquisition, but PCA-treated rats did not differ from controls in their retention performance when tested 24 hr after training. In the dark/light box test pretraining administration of PCA caused a dose-dependent impairment of both active and passive avoidance retention which could not be explained in terms of changes in locomotor activity or behavioural disinhibition at the time of testing or state-dependent retention. Post-training administration of PCA failed to affect avoidance retention in both tasks. The drug was found to impair memory retrieval in a dose- and time-dependent fashion in the one-way active but not in the passive avoidance test. Pretraining administration of PCA produced a progressive loss of passive and active avoidance performance at increasingly longer retention intervals. The present results suggest that serotonin has dual effects on processes underlying learning and memory involving effects on both associative and non-associative learning processes in the rat. The time-dependent loss of memory retention following 5-HT release indicates that serotonin has a role in the way information is processed in the brain.     

Interactions between angiotensin II and baclofen in shuttle-box and passive avoidance performance

In experiments on male rats, we established that angiotensin-II (AT II) at a dose of 0.1 micrograms injected intracerebroventricularly immediately after training improved memory when retention tests (active and passive avoidance) were given 24 hours later. Baclofen at doses of 2, 5 and 10 mg/kg injected intraperitoneally immediately after training also improved retention in both active and passive avoidance tasks. Baclofen at a dose of 20 mg/kg was without effect on active avoidance performance. Combination of AT II and baclofen (2, 5 and 10 mg/kg) facilitated memory in active avoidance as compared to controls, but impaired retention as compared to the AT II-treated group. The impairment of the AT II-improved retention was stronger when the dose of baclofen in the combination was 20 ng/kg. Combination of AT II and baclofen (10 mg/kg) did not impair retention in passive avoidance. These data favor the view that GABA receptors may interfere with the AT II effects on memory consolidation or retention and that interactions of GABA (GABAA and GABAB) receptors with AT II receptors are of importance for memory processes.     

Modulation of memory processing by neuropeptide Y varies with brain injection site

Neuropeptide Y (NPY) is a 36 amino acid peptide which was shown to enhance memory retention, recall and prevent amnesia induced by either scopolamine or anisomycin. In this study, we examined the effects of NPY administration into 6 areas of the mouse brain on memory retention for footshock avoidance training in a T-maze. NPY was injected into the rostral and caudal hippocampus, amygdala, caudate, septum and thalamus shortly after training. NPY improved retention when injected into the rostral portion of the hippocampus and septum, impaired retention in the caudal portion of the hippocampus and amygdala and had no effect in the thalamus and caudate. NPY was ineffective at either improving or impairing retention when injected 24 h after training, thus demonstrating that the effects of NPY on retention were time-dependent and not due to proactive effects on retention test performance per se. In addition, NPY had no effect on retention when injected into overlying cortical areas. NPY antibody impaired retention when administered into the rostral hippocampus and septum; it improved retention in the caudal hippocampus and amygdala. Thus NPY antibody had the opposite effect to that of NPY on memory retention suggesting that NPY has a physiological role as a modulator of memory processing within specific anatomical areas of the central nervous system.     

Arginine-vasopressin content of hippocampus and amygdala during passive avoidance behavior in rats

Arginine-vasopressin (AVP) is involved in memory processes. The memory effects of AVP are mediated by neuronal mechanisms taking place in limbic-midbrain structures. Therefore, immunoreactive AVP (IR-AVP) was measured in hippocampus and amygdala of male Wistar rats during acquisition and retention of passive avoidance behavior.

IR-AVP concentration was decreased in the hippocampus immediately after the learning trial while IR-AVP content of the amygdala was not affected.

Animals that showed the passive avoidance response (good avoiders) at the 24 h or 120 h retention test had a reduced IR-AVP concentration in the hippocampus immediately after the test. However, IR-AVP content of the hippocampus was not different from that of non-shocked control animals when measured immediately before the 120 h retention test. Poor avoiders that showed only minor avoidance behavior did not differ in hippocampal IR-AVP content from non-shocked control animals. IR-AVP content of the amygdala was also not altered after the retention session.

These effects on IR-AVP content could only be shown in animals that were trained and habituated to the passive avoidance procedure. Such trained and habituated animals had an IR-AVP level in the hippocampus which did not differ from that of animals that were left undisturbed until sacrifice. When the animals were not trained, but place for the first time in the passive avoidance apparatus without being exposed to the learning trial, the hippocampal IR-AVP content was reduced. Under these circumstances additional exposure to the electric footshock did not lead to a measurable further decrease in IR-AVP content of the hippocampus. Again, IR-AVP content of the amygdala was not affected. It is proposed that learning and retention of a passive avoidance response is associated with a reduction in hippocampal IR-AVP content. The reduction ppossibly reflects increased secretory activity at the peptidergic terminal. This AVP released at the terminal might be instrumental in facilitating memory formation.     

Dehydroepiandrosterone and its sulfate enhance memory retention in mice

Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), major naturally occurring precursors of both androgenic and estrogenic steroids, were shown in the present study to have convincing memory enhancing effects in mice. Post-training intracerebroventricular (i.c.v.) administration of DHEA in dimethylsulfoxide (2 microliters) prevented the amnesia for footshock active avoidance training (FAAT) caused by the same volume of dimethylsulfoxide alone. DHEAS significantly enhanced retention of FAAT in weakly trained mice whether injected i.c.v. or s.c. immediately post-training or given in the drinking water for a 2-week period. In the latter instance DHEAS was shown to facilitate retention of FAAT without enhancing acquisition. The maximally effective doses were: i.c.v., 162 ng/mouse; s.c., 700 micrograms/mouse; and oral, 1.45 mg/mouse/day. DHEAS administered i.c.v. occluded the amnestic effects of anisomycin (inhibitor of protein synthesis) and scopolamine (muscarinic cholinergic antagonist). There was a time-dependence of the facilitatory effects of post-training i.c.v. administration of DHEAS on retention of FAAT, significant enhancement of retention being observed when it was given either immediately (within 2 min) or at 30 and 60 min after training, but not at 90 or 120 min. DHEAS given i.c.v. also improved retention for step-down passive avoidance. In all instances, dose-dependent inverted U curves were obtained in a manner typical for memory enhancing substances. At a practical level, these experiments open new possibilities for the development of substances that may help in alleviating amnesic disorders in man.     

Differential effects of tumor necrosis factor-alpha co-administered with amyloid beta-peptide (25-35) on memory function and hippocampal damage in rat

Effects of concurrent intracerebroventricular administration of amyloid-beta peptide 25-35 (Abeta(25-35)) and the proinflammatory cytokine tumor necrosis factor-alpha (TNFalpha) to rats were investigated. A battery of behavioral tests including radial arm maze, passive avoidance, elevated plus-maze and forced swim test as well as histological methods were used. A single administration of Abeta(25-35) induced delayed behavioral deficits manifested in reference and working memory disturbances in the radial maze task involving spatial memory. However, no effects of Abeta(25-35) on learning or retention in a passive avoidance test could be revealed. Abeta(25-35) appeared to decrease anxiety without affecting depression-like behavior in the rats. Abeta(25-35)-induced cognitive deficits could be related to the moderate neuronal cell loss found in the hippocampal CA1 field. Though administration of TNFalpha did not impair learning and memory of rats in the radial maze, it induced gross changes in their behavior during passive avoidance training. Though TNFalpha did not protect against Abeta(25-35)-induced neuronal cell loss in the CA1 field of hippocampus, co-administration of TNFalpha with Abeta(25-35) resulted in an improvement of reference memory impaired by the amyloid peptide, but not of working memory.     

Is acetylcholine involved in memory consolidation of over-reinforced learning?

Systemic administration of anticholinergic drugs produces amnesia. To determine whether this effect can be prevented by increasing the magnitude of the learning experience, independent groups of rats were trained in passive avoidance, using a 3.0-mA footshock, and then injected with scopolamine (2, 4, 6, 8 or 12 mg/kg). When retention of the task was evaluated, a dose-dependent amnesic effect was found. When footshock intensity was increased to 6.0 and 9.0 mA, injections of 8 and 12 mg/kg of scopolamine did not produce memory impairments. These findings indicate that acetylcholine plays an important role in consolidation of passive avoidance, but it does not seem to be involved in memory processes when the magnitude of the negative reinforcer is increased.     

Zaprinast consolidates long-term memory when administered to neonate chicks trained using a weakly reinforced single trial passive avoidance task

A weakly reinforced variant of the single trial passive avoidance task developed for the day-old chick typically fails to consolidate long-term memory. However, administration of zaprinast, a phosphodiesterase (PDE) type 5 inhibitor, (ic; 10 microl/side) immediately post-training resulted in a dose-dependent increase in retention at test 180 min post-training. Further, 100 microM zaprinast resulted in high levels of retention at test 180 min post-training when administered from 10 min before training to 10 min after training. Finally, 100 microM zaprinast, when administered immediately post-training, resulted in the consolidation of long-term memory at a number of times of test extending as late as 24 h post-training. Inhibition of PDE type 5 is known to increase cellular cGMP levels. Previous investigations using a strongly reinforced variant of this task have suggested a role for cGMP in memory retrieval, we now postulate that cGMP is also necessary for memory formation in chicks trained using passive avoidance.     

GABA(A) receptor blockade enhances memory consolidation by increasing hippocampal BDNF levels

Memory consolidation is the process by which acquired information is converted to something concrete to be retrieved later. Here we examined a potential role for brain-derived neurotrophic factor (BDNF) in mediating the enhanced memory consolidation induced by the GABA(A) receptor antagonist, bicuculline methiodide. With the administration of an acquisition trial in na?ve mice using a passive avoidance task, mature BDNF (mBDNF) levels were temporally changed in the hippocampal CA1 region, and the lowest levels were observed 9?h after the acquisition trial. In the passive avoidance task, bicuculline methiodide administration within 1?h of training but not after 3?h significantly increased latency time in the retention trial 24?h after the acquisition trial. Concomitantly, 1?h post-training administration of bicuculline methiodide, which enhanced memory consolidation, significantly increased mBDNF levels 9?h after training compared to those of the vehicle-treated control group. In addition, exogenous human recombinant BDNF (hrBDNF) administration 9?h after training into the hippocampal CA1 region facilitated memory consolidation confirming that the increase in mBDNF at around 9?h after training plays a key role in the enhancement of memory consolidation. Moreover, the increases in latency time and immediate early gene expressions by bicuculline methiodide or hrBDNF were significantly blocked by anisomycin, a protein synthesis inhibitor, K252a, a tyrosine receptor kinase (Trk) inhibitor, or anti-TrkB IgG. These findings suggest that the increase in the level of mBDNF and its function during a restricted time window after training are required for the enhancement of memory consolidation by GABA(A) receptor blockade.     

Effects of intracerebroventricular administration of calcitonin gene-related peptide on passive avoidance behaviour in rats.

The effects of different doses of calcitonin gene-related peptide (CGRP) on passive avoidance behaviour were studied in male rats following its intracerebroventricular (i.c.v.) administration. Treatment with doses of 200 ng, 300 ng, 500 ng or 1 microgram was performed prior to learning, immediately and 6 h after the learning session and 30 min before the 24 h retention test. CGRP enhanced the avoidance latency in a dose-dependent manner at each time studied, with the exception of 6 h after the learning session. It is concluded that CGRP might be able to lengthen the passive avoidance latency by facilitating learning and memory formation.     

Effects of peripherally administered arginine-vasopressin on learning, retention and forgetting in mice

The effects of peripheral injections of (Arg)-vasopressin were investigated on different stages of memory processes using an appetitive visual discrimination task and a one-trial passive avoidance conditioning in mice. The peptide was administered at one of two doses: 50 micrograms/kg or 25 micrograms/kg. The main effects of vasopressin were observed only for the higher dose. Concerning pre-session vasopressin administration in the visual discrimination task, the effect of the peptide seemed to depend on the level of learning reached at the time of treatment. Indeed, we observed a deleterious effect of vasopressin on learning capacities when the peptide was administered before the first learning session, a bimodal effect (either an improvement or an impairment) on performance when the peptide was administered before the second learning session and an important enhancement of retention performance when the peptide was administered before the retention session, performed 24 days after training. When post-session vasopressin administration was assessed, an improvement of performance was observed indicating a facilitatory effect of vasopressin on consolidation processes. When passive avoidance conditioning was used, an enhancement of retention performance was registered only when the peptide was injected before the retention session at the 50 micrograms/kg dose. No facilitation was observed for the 25 micrograms/kg dose whatever the experimental condition was, i.e. post-learning or pre-retention injection. In order to test eventual non-specific effects of vasopressin, the influence of the peptide on locomotor activity was assessed before the two doses. The results show an important reduction of locomotor activity with the 50 micrograms/kg dose, during 4 h following vasopressin injection. No effect was observed with the 25 micrograms/kg dose. The whole results suggest that vasopressin-induced hypoactivity can directly influence the subsequent learning performance when the treatment was performed in pre-session situations. However, when the level of information is sufficient and beyond the direct effect of the drug, a memory effect may be considered with the 50 micrograms/kg dose independently from the locomotor effect, when the treatment was delivered during consolidation period (post-session) or in long-term retrieval situation (pre-session).     

NBQX does not affect learning and memory tasks in mice: a comparison with D-CPPene and ifenprodil

The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline (NBQX) did not impair working memory measured as alternation behavior in the Y-maze in mice. No depressant effect on alternation was detected even when NBQX impaired locomotion measured as the total number of arm entries. Similar profile of action in the Y-shaped maze was observed after administration of an anti-ischemic drug ifenprodil. In contrast, the N-methyl-D-aspartate (NMDA) antagonist (D-(E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylate (D-CPPene) impaired spontaneous alternation. In the step-through passive avoidance task, mice were trained to avoid dark compartment entry. NBQX and ifenprodil did not impair learning in this task when administered before or immediately after training. In contrast, D-CPPene disturbed acquisition when administered before but not immediately after training or before retention test. These observations suggest that AMPA receptors are not critically involved in the formation of spatial working memory and acquisition (storage) in the passive avoidance, and have no effect on recall (retrieval) from long-term memory.     

Effects of oral administration of the competitive N-methyl-D-aspartate antagonist, CGP 40116, on passive avoidance, spatial learning, and neuromotor abilities in mice

The effects were investigated of the potent competitive N-methyl-D-aspartate (NMDA) receptor antagonist CGP 40116[D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid] on the performance of mice in water maze and passive avoidance tasks, and in wire suspension, rotarod, and cage activity tests. The drug was administered per os (p.o.) in its anticonvulsant dose range. CGP 40116 dose-dependently impaired passive avoidance learning when given before, but not when given after training. The antagonist (5, 10, and 20 mg/kg, administered 4 h before each training session) dose-dependently affected water maze acquisition, and impaired retention test performance in both hidden- and visible-platform water maze tasks. In addition, the drug dose-dependently decreased swimming speed during water maze acquisition. Repeated administration of CGP 40116 (20 mg/kg, p.o.) persistently decreased cage activity and wire suspension test performance, whereas motor coordination and equilibrium on the rotarod apparatus remained unimpaired. In our administration protocol, no tolerance was found to the effects of the drug on passive avoidance learning and neuromotor abilities. The parallel effects of CGP 40116 on memory and motor performance are discussed, and it was concluded that the antagonist impairs neuromotor abilities and also induces memory impairments which cannot be entirely reduced to motor interference.     

Corticosterone enhances long-term retention in one-day-old chicks trained in a weak passive avoidance learning paradigm

Glucocorticoids are released during learning situations and can trigger neural actions through binding to receptors in different brain areas. The possible role of a glucocorticoid action in long-term memory formation was studied, in day-old chicks, by using a passive avoidance task which chicks otherwise only retain for a few hours (<10) after training. Thus, we examined the effects of intracerebral corticosterone administration on retention 24 h posttraining. The results showed that chicks injected with corticosterone (1 μg) at either 15 min pretraining or at 5, 30, 60 min (but not 120, 180 or 360 min) posttraining retained the passive avoidance response when tested 24 h posttraining. Studies with specific mineralocorticoid or glucocorticoid receptor antagonists (RU 28318 or RU, 38386 respectively) indicated that this increas in retention by corticosterone might be mediated through glucocorticoid receptors. In order to assess whether the facilitatory effect of corticosterone was mediated through an effect on protein synthesis mechanisms, the protein synthesis inhibitor anisomysin was administered prior to corticosterone. However, this treatment only partially attenuated the effect of the steroid, suggesting that corticosterone may influence other cellular processes involved in the formation of long-term memory for the avoidance behaviour.     

Effects of intra-amygdala injections of NMDA receptor antagonists on acquisition and retention of inhibitory avoidance

These experiments examined the effects of intra-amygdala injections of NMDA receptor antagonists on the acquisition and retention of inhibitory avoidance. In Expt. I, rats received bilateral intra-amygdala injections of the NMDA antagonists D,L-AP5 (1-10 micrograms), D-AP5 (0.03-1 micrograms), CPP (0.125 or 0.375 microgram), or MK-801 (0.2 or 0.5 microgram) prior to training in a continuous multiple-trial inhibitory avoidance (CMIA) task. Acquisition of the task was not significantly affected by any of the drug injections. In contrast, all three competitive antagonists, D,L-AP5, D-AP5 and CPP, produced dose-dependent impairment of 48 h retention performance. Although the MK-801 injections did not significantly impair retention performance, the retention scores of the 0.5 microgram MK-801 group were bimodally distributed, indicating retention impairment in a subgroup of the animals given that dose. Intra-amygdala injections of 3 or 10 micrograms D,L-AP5 did not affect footshock sensitivity (Expt. II) or locomotor activity (Expt. III) and their retention-impairing effects were not due to induction of state dependency (Expt. IV). The retention-impairing effects of intra-amygdala injections of NMDA antagonists were not due to diffusion of the drugs dorsally: injections of 1 microgram D-AP5 into the striatal area directly above the amygdala impaired acquisition but not retention performance (Expt. V). The retention-impairing effects of 1 microgram D-AP5 or 0.5 microgram MK-801 were attenuated by giving additional training to the animals shortly after receiving intra-amygdala injections (Expt. VI). The implications of these findings for hypotheses concerning amygdala function in learning and memory are discussed.     

Hippocampal CRF,NE, and NMDA system interactions in memory processing in the rat

In the present study, we investigated the neural mechanisms of corticotropin-releasing factor (CRF) and the interactions among CRF, norepinephrine (NE), and N-methyl-D-aspartate (NMDA) systems in the dentate gyrus (DG) of hippocampus in modulating the memory process of rats. One-way passive avoidance task was adopted. Results indicated that CRF (80 ng), when directly injected into the DG, consistently and significantly enhanced memory retention in rats. The noradrenergic neurotoxin DSP-4, at a high dose (4 μg), impaired memory. DSP-4 at a moderate dose (2 μg), which did not affect retention alone, antagonized the memory-enhancing effect of CRF. Similarly, the ß-adrenergic antagonist propranolol, at a high dose (8 μg), reduced retention. At a low dose (80 ng), which did not markedly affect retention by itself, propranolol also prevented the memory-improving effect of CRF. Moreover, direct NE infusions to the DG significantly improved retention performance in a dose-sensitive manner. Coadministration of CRF and NE did not further enhance retention. These results together suggest that CRF and NE facilitated memory probably through the same instead of independent mechanisms. In contrast, the selective NMDA receptor antagonists 2-amino-5-phosphonopentanoate (AP5) and MK801, at high doses markedly impaired memory retention (0. 8 and 3. 2 μg for AP5, 2 and 10 μg for MK801). At a dose of MK801 that did not significantly alter retention alone (80 ng), it completely blocked the memory-facilitating effect of CRF. These results indicate that CRF enhanced memory indirectly through NMDA receptor mediation also. Finally, MK801 at 80 ng also successfully antagonized the memory-facilitating effect of NE in the DG. We have demonstrated that MK801, at the dose chosen for interaction studies, did not markedly alter locomotor activity. These results together suggest that CRF, through a presynaptic facilitation mechanism, possibly facilitates NE release in the DG: increased NE release and stimulation of ß-adrenergic receptors in the DG result in NMDA receptor activations in the same area. This sequence of events enhance the memory consolidation process in the hippocampus and explained the neural mechanism of CRF in facilitating retention performance in rats. The same neuropeptide/neurotransmitter interactions may have other physiological and neuropathological implications. © 1993 Wiley-Liss, Inc.     

Nociceptin system plays a role in the memory retention: involvement of naloxone benzoylhydrazone binding sites.

We investigated the role of nociceptin system in learning and memory in mice. The deficiency of nociceptin receptors and nociceptin itself did not affect the alternation behavior in the Y-maze test. In the passive avoidance test, the step-through latencies of nociceptin receptor knockout mice were longer than those of wild-type mice. Nociceptin shortened the step-through latency in wild-type mice. This impairment on passive avoidance task was reversed by naloxone benzoylhydrazone (NalBzoH), indicating that the amnesic effects of nociceptin may be mediated through the NalBzoH recognition sites. These suggest that nociceptin system plays an important role in the memory retention of passive avoidance task, and NalBzoH-recognized sites are involved in nociceptin-induced impairment of the memory retention.     

Effects of concurrent manipulations of cholinergic and noradrenergic function on learning and retention in mice

Interactions between the neuromodulators acetylcholine and norepinephrine (NE) have been reported in both developmental neural plasticity and learning and memory. In a test of the generality of this phenomenon, we assessed the amnestic effects of the muscarinic antagonist scopolamine in normal and NE-depleted mice. Pretraining administration of scopolamine impaired 24-h retention of inhibitory (passive) avoidance training (at doses of 0.1, 0.3 and 1.0 mg/kg) and the acquisition of place-training in a water maze (at a dose of 1.0 mg/kg). NE depletion resulting from systemic administration of DSP-4 did not affect performance on these tasks and did not significantly alter the effects of scopolamine. NE depletion did, however, impair the retention of place learning when mice were retested 16 days after initial training; and this impairment in the retest was additive with one observed in mice originally trained under scopolamine. Normal acquisition but rapid forgetting has also been reported in aged rodents, who display deterioration of the noradrenergic system. Thus, observation of a similar pattern of performance consequent to experimental NE depletion suggests a role for noradrenergic dysfunction in age-related memory decline.     

Effects of NMDA and AMPA Receptor Antagonists on Corticosterone Facilitation of Long-term Memory in the Chick

Long-term memory formation for a weak passive avoidance task in day-old chicks is facilitated by corticosterone administration. Since (i) glutamatergic systems, through different receptor types, play a key role in learning and memory processes, and (ii) glucocorticoids increase glutamate concentrations in learning-related regions of the mammalian brain, we reasoned that glutamatergic activation might be a mechanism by which corticosterone facilitates the formation of an enduring memory. To assess this hypothesis, long-term retention was evaluated in chicks trained on a weak passive avoidance task and intracerebrally injected with NMDA and a-amino-3-hydroxyd-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists (MK-801 and 6-cyano-7-nitroquinoxaline-2,3-dione) with regard to training and corticosterone injection respectively. The results indicated that either of the antagonists prevented the facilitating effect of corticosterone when administered before the training trial, but failed to interfere with the steroid effect when injected before corticosterone administration in the post-training period, suggesting that their early effectiveness was not related to corticosterone-induced actions but to training-triggered mechanisms. In addition, administration of the AMPA antagonist, 5.5 h after training, was also effective in impairing the long-term memory-potentiating effect of corticosterone. These results support the view that corticosterone facilitates the formation of an enduring memory in this learning model, through the modulation of late events during the consolidation period, including the activation of the AMPA receptor type.     

Pyroglutamic acid improves learning and memory capacities in old rats

The effects of the arginine salt of pyroglutamic acid (2-oxo-pyrrolidone carboxylic acid, PCA) on learning and memory capacities of old rats were studied in a subchronic treatment schedule (i.p. injection of 0.1 and 1 g/kg/day for 15 days). The acquisition and extinction of active avoidance behaviour were studied in a pole-jumping test situation. The retention of passive avoidance response was examined in a step-through passive avoidance task. PCA facilitated the rate of acquisition of pole-jumping response, and inhibited the extinction of the response. The dose of 1 g/kg was more potent than 0.1 g/kg in this respect. Also in the passive avoidance task, the treatment with PCA was followed by an improvement of avoidance retention. These results indicate that PCA is a behaviourally active compound in that it improves learning and memory capacities in old rat.