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A characterization of approach and avoidance learning in high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rats.

BACKGROUND: This study was undertaken as one of a series of experiments designed to examine basic behavioral characteristics present in rats bred specifically for alcohol preference. The basic premise for these experiments has been the idea that alcohol-preferring and -nonpreferring rats may differ in basic activation and inhibition control mechanisms that govern behavior and that different lines of alcohol-preferring rats may demonstrate differential deficits in behavioral activation and behavioral inhibition tendencies. In the present experiment, conditioned approach and avoidance behaviors were studied in alcohol-naïve high-alcohol-drinking (HAD), low-alcohol-drinking (LAD), and N/NIH rats to evaluate behavioral activation in this line of rats. METHODS: High alcohol drinking (HAD1), low alcohol drinking (LAD1), and N/Nih stock rats were trained to press a response bar during a tone signal to avoid a mild foot shock or receive a food reward. In addition, HAD2 and LAD2 rats, independently-bred replicate lines of the HAD1/LAD1 rats, were trained on the avoidance task. RESULTS: Although the HAD1 rats easily learned the appetitive version of the bar-pressing task, they did not learn the avoidance response. The LAD1 and N/Nih rats learned both the approach and the avoidance tasks normally. Similar to HAD1 rats, the HAD2 rats did not learn the avoidance response whereas LAD2 rats showed significant avoidance performance levels. CONCLUSIONS: The present data demonstrated that both HAD1 and HAD2 rats had a rather specific behavioral activation deficit: although they easily learned to press a bar to receive food reinforcement, they did not learn to press the bar to avoid a foot shock. We speculate that this failure to learn the avoidance response may be related to heightened anxiety in the HAD rats and that this excessive anxiety may lead to the development of high levels of alcohol consumption in these selectively bred rats.

Alcoholism↗

Cerebellar interpositus nucleus lesions disrupt classical nictitating membrane conditioning but not discriminative avoidance learning in rabbits.

Cerebellar interpositus nucleus lesions were given to 14 rabbits trained in two behavioral paradigms; discriminative avoidance conditioning of locomotor behavior and classical nictitating membrane conditioning. Bilateral lesions that prevented acquisition of the classically conditioned response on both the left and right side failed to affect the acquisition or performance of the conditioned discriminative avoidance response. The results are discussed in terms of differences in neural substrates that apparently subserve the two forms of learning.

Animals↗

Nitric oxide synthetase inhibition hinders facilitation of active avoidance learning by nicotine in rats.

Nicotine produces dose-dependent enhancement of performance in an active avoidance test, and also increases the levels of NO2- and NO3-, which are stable metabolites of nitric oxide (NO), in various brain regions of rats. On the basis of these two observations, we hypothesized that the beneficial effect of nicotine on learning could result from increased NO in relevant brain regions. We therefore tested active avoidance performance in rats given L-Nomega-nitroarginine (L-NA) to inhibit NO synthetase (NOS) prior to nicotine administration. Male Sprague-Dawley rats received L-NA (30 or 50 mg/kg), nicotine (0.4 mg/kg), saline or combinations of these treatments before learning trials. Rats were also tested on the inclined plane, to assess the possible effects due to impairment of motor function by drug treatments on active avoidance learning. L-NA treatment impaired the acquisition of active avoidance learning, and this defect was partially overcome by the co-administration of nicotine. Nicotine facilitated learning and significantly increased the number of correct responses. The threshold for the effect of NOS inhibition on performance exceeded 30 mg/kg L-NA, whereas 50 mg/kg impaired learning and also eliminated the nicotine-induced enhancement of learning. On the fifth day of learning trials, no facilitation of learning by nicotine was observed in rats receiving either dose of L-NA. Our results suggest that NO is involved in the facilitation of active avoidance learning by nicotine.

Animals↗

Male and female C57BL/6 mice respond differently to diazepam challenge in avoidance learning tasks.

Benzodiazepines (BZ) impair learning and memory performance of animals. The goal of this study was to examine sex differences in the effects of diazepam on learning and memory of C57BL/6 mice in avoidance paradigms. Male and female C57BL/6 mice were tested in the one-way active avoidance, step-down passive avoidance, and foot-shock pain threshold tasks, following administration of vehicle or diazepam (1 mg/kg). No substantial sex or drug effects on the threshold of the pain response to shock were found. There were no significant differences in avoidance performance between vehicle-treated male and female mice while 1 mg/kg of diazepam produced opposite effects on performance of males and females in both tasks. Diazepam-treated females learned faster in the active avoidance task and showed stronger retention in the passive avoidance task. In contrast, diazepam impaired learning of males in the active avoidance task and had no effect on their performance in the passive avoidance task. Diazepam-induced impairment in males was not due to higher sensitivity to the sedative effect of diazepam as females were more sedated than males on the first trial of the passive avoidance task. Our data showed that sedative and amnesic effects of BZs are not tightly linked. This study also suggests that cognitive effects of BZs in rodents could be sex dependent and highlight the importance of using both sexes in studies on behavioral effects of psychoactive drugs.

Animals↗

Impaired passive avoidance learning in mice lacking central neuronal nicotinic acetylcholine receptors.

The nicotinic cholinergic system influences cognition, anxiety, locomotion, and addiction by acting upon nicotinic acetylcholine receptors (nAChRs). To date, there are 12 known neuronal mammalian nAChR subunits leading to a rich pharmacological diversity that is difficult to attribute to specific subunits. We generated alpha7-beta2 nAChR double mutant mice by breeding to investigate the effect of a minimal number of nAChRs in the CNS. These mice have been used to determine the role these receptor subunits play in a variety of behaviors. A battery of behavioral tests was used to determine the effect of the mutation in anxiety, locomotor activity, startle response, pre-pulse inhibition, motor coordination and learning and memory. Mice lacking both the alpha7 and the beta2 nAChR subunits displayed impaired learning and memory performance in a passive avoidance test and showed enhanced motor performance on the rotarod.

Analysis of Variance↗

[Effect of conditioned-reflex bilateral avoidance learning on lipid components of the rat brain].

The active avoidance training of rats resulted in a depletion of lipid peroxidation (LPO) products in cerebral cortex. LPO inhibition was also shown in cerebral cortex of "active control" group receiving +non-combined stimuli (the effect of short-term stress). LPO inhibition was more pronounced in rats staining a training criterion compared to rats which received combined stimuli but did not reach the criterion. In the active control group LPO inhibition was accompanied by total phospholipids accumulation and cholesterol depletion in cortical lipid extracts. Irrespective of attaining the criterion in all rats trained for active avoidance the accumulation of cholesterol was seen. Active avoidance training affected also the phospholipid composition of cerebral cortex.

Animals↗

Active and passive avoidance learning in homozygous D.I. Brattleboro rats.

In homozygous D.I. rats and in Long-Evans controls the contemporaneous evolution of learning and retention of active and passive avoidance responses was studied by means of the light-dark box test. Passive avoidance performance of homozygous D.I. rats was almost equal to that of control subjects, while their active avoidance performance showed a significant deficit. Also, in homozygous D.I. rats the duration of the first freezing after being placed in the apparatus was consistently longer than in control Ss. The longer duration of this inhibitory behavior has been taken as an indication of a diminished ability of homozygous D.I. rats to respond to stress. The possible role of this diminished response to stress in determining the active avoidance deficit is discussed.

Animals↗

A comparison of shock avoidance learning in headless cockroaches in leg-lifting and lowering task.

Headless cockroaches were trained either to lift or to lower the prothoracic leg to avoid electric shocks. The learning process in both cases was very distinct. However, the learning performance in the lifting was better than in the lowering task. The reason for this poorer learning in the lowering task is due to the unconditioned leg raising movement of the animals to electric shocks. This unconditioned response affects the headless cockroaches avoid shocks in the lifting task by escape learning, whereas they avoid shocks in the lowering task by true avoidance learning. Injection of 30 microliter of Ringer's solution has no significant effect on the learning process in the lifting task. In the lowering task, however, Ringer's solution impairs the learning ability considerably. Crude extract of corpora cardiaca strongly inhibits the learning of both tasks.

Animals↗

Intra-amygdala kinase inhibitors disrupt retention of a learned avoidance response in rats.

To assess the involvement of intra-amygdala kinase activity in aversively motivated learning, rats received intracranial injections of polymixin B sulfate (PMXB)--a protein kinase C (PKC) and calcium/calmodulin-dependent kinase II inhibitor--immediately after inhibitory avoidance training. When tested 48 h later, retention was significantly impaired relative to vehicle-injected controls. Delayed injections (2 h posttraining) and injections made dorsal to the amygdala were ineffective. Immediate posttraining injections of the more selective PKC inhibitor, NPC 15437, also impaired retention. These results suggest that intra-amygdala protein phosphorylation must occur soon after training for learned avoidance responses to be successfully retained.

Amygdala↗