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Ethanol consumption improves avoidance learning in rats: role of deprivation interval.

Voluntary oral self-administration of ethanol in rats has been used to model ethanol consumption and abuse in human beings, with contradictory results. The purpose of the current study was to assess the effect of voluntary ethanol consumption on acquisition of a lever press escape/avoidance task in rats. Male Wistar rats were exposed to ethanol in a limited-access procedure, and either 1 day or 10 days after their last ethanol exposure, animals received a 4-h lever press escape/avoidance session. Control animals were not exposed to ethanol at any time. Animals in the 1-day ethanol-deprivation group performed significantly better than did the other two groups with respect to avoidance responding. There were no group differences in number of lever presses during a safety period, a measure of anxiety. Further, we obtained a significant negative correlation between behavioral performance and change in ethanol consumption after the escape/avoidance session, as well as a significant positive correlation between baseline ethanol consumption and avoidance performance. Results are discussed in terms of the potential neural mediators of the improved avoidance effect in animals in the 1-day ethanol-deprivation group.

Alcohol Drinking↗

Nerve growth factor affects passive avoidance learning and retention in developing mice.

The present studies investigate the effects of early nerve growth factor (NGF) administration on the ontogenetic profile of learning and retention capacities in mice. The learning paradigm used required the animals to withhold an escape response from a vibrating platform to avoid a punishment (step-down passive avoidance). In Experiment 1, acquisition of step-down passive avoidance was essentially the same in 11- and 15-day-old mice whereas only the latter showed significant retention after 24 h. In younger animals, data pointed to a facilitating effect of familiarization with the test environment. In Experiment 2 ICV NGF treatment on postnatal day 9 increased step-down latencies in both reinforced and nonreinforced pups on day 11. Moreover, NGF mice exposed in nonreinforcement condition on day 11 failed to acquire the avoidance response 24 h later, suggesting that the treatment anticipated the appearance of latent inhibition. Results of Experiment 3, investigating the effects of different durations of preexposure to the test apparatus on passive avoidance acquisition 24 h later, supported the specificity of NGF effects on the emergence of latent inhibition. These findings suggest that neural populations responsive to NGF trophic effect are involved in the maturation of early learning and retention capacities in rodents.

Animals↗

[Effect of piracetam on passive avoidance learning in ethanol-treated mice].

Mice received pre- and postnatal drinking water containing 20% ethanol. Ethanol treatment significantly impaired learning, reflected by shorter latency to enter the dark compartment of the apparatus. This effect could be antagonized by the administration of twice daily 100 mg/kg piracetam for ten days. The ethanol treatment and the administration of piracetam did not affect the step-through latencies in the training situation.

Animals↗

Behavioral effects of exposure to nuclear magnetic resonance imaging: I. Open-field behavior and passive avoidance learning in rats.

The effect of exposure to the magnetic and radio-frequency fields associated with Nuclear Magnetic Resonance Imaging (MRI) on two standard animal behavior tests, was examined in rats. In the first experiment male rats were given a baseline open-field test and 48 hrs later exposed for 22.5 min to a MRI procedure, a sham imaging procedure, or a control condition. Immediately after this exposure period a second open-field test was administered. All animals were given 4 more daily exposures to their respective treatment conditions and after the last exposure period a third open-field test was given. Analysis of open-field ambulation, rearing, and defecation responses indicated no significant effect of exposure to MRI on these behaviours. In a second experiment rats were conditioned in a step-down passive avoidance task and then exposed for 23.2 min (48 hrs later) to MRI, sham imaging, or control conditions. Retention tests for the passive avoidance response were administered after the first and fifth daily exposure to the experimental treatment conditions. No significant effects of the treatment conditions on retention of the avoidance response were obtained and a third retention test 3 months after the second test, also failed to provide any evidence for treatment effects. These results fail to provide any evidence for short or long term behavioral changes in animals exposed to MRI.

Animals↗

Effects of endogenous morphine deprivation on memory retention of passive avoidance learning in mice.

Memory and the processes of learning in mammals are well known to be affected by opioid agonists such as morphine, which has been proven to interfere and cause amnesia. The presence of endogenous morphine has been demonstrated in various tissues from mammals to invertebrates. In this study, we have investigated the effects caused by in-vivo immunodepletion of endogenous morphine on working memory under different experimental conditions. When mice were submitted to fasting, a stress condition, acquisition and consolidation of memory were significantly impaired compared to controls. This was demonstrated by a decrease in entry latency into the dark room in the retention session of the passive avoidance test. This effect was significantly reversed to baseline values when endogenous morphine was depleted from the extracellular brain space. These findings support a role for endogenous morphine in weakening memory processes under stress conditions.

Animals↗

Effect of morphine and naloxone on shock avoidance learning in headless cockroaches (Periplaneta americana L.).

Systemic administration of high doses of morphine (56 micrograms morphine/g body weight) or of naloxone (54 micrograms naloxone/g body weight) results in a significant improvement of shock avoidance behavior in headless cockroaches. In both cases the learning parameter stimulation time (time during which an animal receives shocks) is significantly decreased. The behavioral parameters, stimulation rate (activity) and mean stimulation duration (shock responsiveness), as the two factors of the stimulation time considered individually, do not significantly change with morphine. Only the responses of both parameters together give the significant decrease of stimulation time (improvement of shock avoidance behavior) as mentioned above. However, the administration of naloxone causes a significant shortening of the mean stimulation duration indicating that these animals avoid the shocks by learning to lift their legs more quickly out of electrified saline in order to terminate the shocks (escape learning). Combined administration of both drugs together also causes a significant improvement of the leg-lifting response even at lower doses (morphine: 0.56 microgram plus naloxone: 0.54 microgram/g; morphine: 0.0056 microgram/g plus naloxone: 0.0054 microgram/g). Although the various effective doses of these drugs administered in combination have similar effects on the stimulation time, they affect the behavioral parameters in different ways. These different actions on activity and shock responsiveness as well as the efficacy of doses smaller than those known from vertebrates are discussed as behavioral evidence of opiate receptors in the cockroach.

Animals↗

Effects of prenatal AZT on mouse neurobehavioral development and passive avoidance learning.

Recent evidence has shown that perinatal administration of zidovudine (AZT) to HIV-infected mothers reduces the risk of maternal-infant transmission of the virus. Treatment of pregnant seropositive women with AZT is becoming a common medical practice, despite the paucity of information about the potential neurotoxic/behavioral-teratogenic effects of AZT on the developing organism. The aim of the present study is to evaluate in mice the short-, medium-, and long-term effects of prenatal exposure to AZT on neurobehavioral development. Pregnant mice were given 0.2, 0.4, and 2.0 mg/ml AZT in drinking water from day 10 of gestation to delivery. Offspring's viability was severely affected in the 2.0 mg/ml AZT group. Thus, behavioral analysis was carried out in offspring of 0.2 and 0.4 mg/ml AZT-treated females only. Some limited but significant alterations were found, such as stunted body weight, delayed appearance of the pole-grasping reflex, and a slight impairment in the acquisition phase of a passive avoidance response. Moreover, sexual differences in some items of the social behavior repertoire appeared to be affected by AZT treatment.

Agonistic Behavior↗

Facilitation of memory retrieval by pre-test morphine and its state dependency in the step-through type passive avoidance learning test in mice.

Amnesia produced by scopolamine and cycloheximide were reversed by morphine given 30 min before the test trial (pre-test), and pre-test morphine also facilitated the memory retrieval in the animals administered naloxone during the training trial. Similarly, pre-test scopolamine partially reversed the scopolamine-induced amnesia, but not significantly; and pre-test cycloheximide failed to reverse the cycloheximide-induced amnesia. These results suggest that the facilitation of memory retrieval by pre-test morphine might be the direct action of morphine rather than a state dependent effect.

Amnesia↗

Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain.

Nicotine affects many aspects of behaviour including learning and memory through its interaction with neuronal nicotinic acetylcholine receptors (nAChR). Functional nAChRs are pentameric proteins containing at least one type of alpha-subunit and one type of beta-subunit. The involvement of a particular neuronal nicotinic subunit in pharmacology and behaviour was examined using gene targeting to mutate beta 2, the most widely expressed nAChR subunit in the central nervous system. We report here that high-affinity binding sites for nicotine are absent from the brains of mice homozygous for the beta 2-subunit mutation. Further, electrophysiological recording from brain slices reveals that thalamic neurons from these mice do not respond to nicotine application. Finally, behavioural tests demonstrate that nicotine no longer augments the performance of beta 2-1- mice on passive avoidance, a test of associative memory. Paradoxically, mutant mice are able to perform better than their non-mutant siblings on this task.

Animals↗

Anterior and medial thalamic lesions, discriminative avoidance learning, and cingulate cortical neuronal activity in rabbits.

Four groups of male albino rabbits were trained to perform a conditioned response (CR, stepping in an activity wheel) to an acoustic (pure tone) conditional stimulus (CS+). A 1.5-2.0 mA shock unconditional stimulus (US) delivered through the grid floor of the wheel was administered 5 s after CS+ onset, but stepping during the CS-US interval prevented the US. The rabbits were also trained to ignore a second tone (a negative conditional stimulus or CS-) of different auditory frequency than the CS+, that was presented in an irregular order on half of the conditioning trials but never followed by the US. One group had bilateral electrolytic lesions in the medial dorsal (MD) thalamic nucleus, a second group had combined bilateral lesions in the MD and the anterior thalamic nuclei, and a third group had no lesions. The fourth group was composed of rabbits with combined lesions that resulted in only partial damage in the anterior and MD nuclei. In all rabbits, multi-unit activity and field potentials were recorded from the cingulate cortical projection targets of the MD and anterior nuclei. The average rate of acquisition in rabbits with MD and partial lesions was not significantly different from that in controls, but the asymptotic performance in rabbits with lesions was significantly impaired, relative to that in controls. None of the rabbits that had the combined MD and anterior thalamic lesions reached the acquisition criterion. The average proportion of trials in which these rabbits performed avoidance responses during their final training sessions was 0.3, compared to 0.8 in controls. The unconditioned response was not significantly affected by the lesions, nor was there any indication that the lesions impaired the sensory processing of the CSs. These results and the massive training-induced neuronal discharges shown in past studies to occur in the limbic thalamic neurons indicate that these neurons are importantly involved in the circuitry that mediates discriminative avoidance conditioning in rabbits. The training-induced neuronal activity in cingulate cortex was dramatically attenuated in rabbits with lesions. Differences in the degree of this attenuation between lesion conditions and with respect to training stages were discussed in relation to a theoretical working model of limbic thalamic and cingulate cortical associative functions.

Acoustic Stimulation↗

Postnatal administration of L-dopa normalizes hypoxia-induced long-term changes in dopamine release from striatum slices and in avoidance learning.

Newborn rats exposed to a mild chronic postnatal hypoxia always displayed at the age of 2-3 months an increased fractional efflux rate of dopamine (DA) from striatum slices combined with a decreased capacity for learning and retention. The protective effect of the administration of L-DOPA on these long-term changes was tested by the injection of L-DOPA 5-30 min prior to the beginning of daily exposure to hypoxia. L-DOPA administration during postnatal hypoxia prevents in a dose dependent manner the long-term effects of postnatal hypoxia as described. This finding supports the hypothesis that long-term changes in DA release and in behaviour due to early postnatal hypoxia may be brought about by changes in the DA-metabolism during a critical period of development.

Animals↗

Effects of histamine and cholinergic systems on memory retention of passive avoidance learning in rats.

In the present study, the effects of the histamine and cholinergic systems on memory retention in adult male rats were investigated. Post-training intracerebroventricular injections were carried out in all the experiments. Cholinoceptor agonist, acetylcholine (1-10 microg/rat) or nicotine (1-10 microg/rat), increased, while a cholinoceptor antagonist, scopolamine (5-20 microg/rat), decreased memory retention. The response to acetylcholine was attenuated by scopolamine. Administration of histamine (5-20 microg/rat) reduced, but the histamine H(1) receptor antagonist, pyrilamine (10-50 microg/rat), and the histamine H(2) receptor antagonist, cimetidine (1-50 microg/rat), increased memory retention in rats. The histamine receptor antagonists attenuated the response to histamine. Histamine reduced the acetylcholine- or nicotine-induced enhancement. The histamine receptor antagonists enhanced the nicotine- or acetylcholine-induced response. Histamine potentiated the inhibitory effect induced by scopolamine. It is concluded that histaminergic and cholinergic systems have opposing effects on memory retention. Also, the histaminergic system elicits an interaction with the cholinergic system in memory retention.

Acetylcholine↗

Effect of amitriptyline on avoidance learning in rats following olfactory bulb ablation.

It has been established that following bilateral olfactory bulb ablation there occurs a performance deficit in rats exposed to aversive learning procedures. Associated with the behavioral deficit, there occurs a reduction in total cortical norepinephrine (NE). If the behavioural deficit observed is a sequitur or correlate of the NE reduction, then drug therapy aimed at increasing NE availability in the cortex should overcome the reduction in performance. Amitriptyline increases NE availability by inhibiting uptake mechanisms and increases the rate of synthesis of NE. Rats, previously bulb ablated, were treated with amitriptyline over a 10 to 14 day period and tested in aversive situations. It was demonstrated that the drug treated rats showed improved performance early in acquisition, and that the performance improvement was maintained when the treatment period was extended to 14 days. These results indicate that amitriptyline was inducing a true pharmacological effect, and that the improved performance could be correlated with increased NE availability in the cerebral cortex.

Amitriptyline↗

Hemispheric lateralization of memory stages for discriminated avoidance learning in the chick.

Memory formation following the one trial discriminated bead task in the chick falls into three stages (short-term, intermediate and long-term memory) that are defined by susceptibility to different classes of drugs. The stages show sharply timed offsets of sensitivity and loss at specific times after inhibition. Recall of the memory in the chick shows cyclical changes that differ in period between left and right hemispheres, and is marked by a series of brief windows of enhanced recall that recur with periods of about 16 and 25 min in the left and right hemispheres respectively. The timing of these 'retrieval events' corresponds, to a large extent, with the timing of the memory stages seen in the visual discrimination task. Here we examine the effects of left or right hemisphere injection of the main agents (glutamate, ouabain and anisomycin) that have been used to characterize the three stages of memory. We show that memory in the left hemisphere is largely responsible for performance at test and that processes involved in its consolidation generate the phases of memory.

Animals↗

CREB phosphorylation coincides with transient synapse formation in the rat hippocampal dentate gyrus following avoidance learning.

Spine density change in the hippocampal dentate gyrus accompanies memory consolidation and coincides with the increased expression of ribosome-rich, hyperchromatic granule cells. Although this suggests increased protein synthesis to be required for synaptic growth in the 5 to 7 h post-training period, little temporal mapping of the associated molecular mechanisms has been done. Here, we demonstrate a similar frequency of hyperchromatic cells in naïve animals and in those sacrificed 6 h post-training, suggesting a transient repression of protein synthesis in the early post-training period. Immunoblot analysis of CREB phosphorylation in the dentate gyrus supported this view, with downregulation from basal levels observed at 2 to 3 h and at 12 h post-training. Protein synthesis reactivation appears to be specific for de novo spine production as no change in spine frequency accompanies the immediate post-training period of depressed protein synthesis. These findings support the view that CREB-mediated gene transcription is a requirement for long-term memory consolidation and may be directly implicated in the process of synaptic growth.

Animals↗

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.

Amphetamines↗

Passive avoidance learning induced change in GAP43 phosphorylation in day-old chicks.

Day-old chicks trained on a single trial passive discriminated avoidance task demonstrated a significant increase in in vitro phosphorylation of a 50 kDa protein in P2M fractions of total forebrain. The increase occurred 30 min posttraining, at a time when previous reports suggest that mechanisms for triggering protein synthesis-dependent long-term memory consolidation are activated. These changes in phosphorylation rates were accompanied by a substantial enhancement of total kinase activity. Immunoblotting studies with monoclonal anti-GAP43 antibody indicate that this protein is GAP43. These results contradict previous reports of a decrease in in vitro GAP43 phosphorylation following the same learning paradigm. A number of procedural differences may account for this discrepancy. The results suggest that changes in the phosphorylation state may be associated with mechanisms triggering long-term memory consolidation.

Animals↗

[The characteristics of shuttle avoidance learning in spontaneously hypertensive and normotensive rats].

In spontaneously hypertensive (strain SHR) and normotensive (strain WKY) rats was studied the elaboration of conditioned reflex of active avoidance in shuttle box. In case when the shuttle box was divided by a partition the SHR rats learned worse than WKY rats. In shuttle chamber without partition the SHR rats, on the contrary, learned better that WKY ones. Such character of interlinear differences can be connected with properties of formation of the instrumental habit of deliverance from electropainful stimulus, because the presence of partition significantly hampered its fulfillment. The obtained results, compared with literature data, testify to the fact that differences of SHR and WKY rats in elaboration of conditioned reflexes are explained basically by the properties of their unconditioned activity and not of the associative processes.

Animals↗