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Experimental data reported here provide evidence that marked defensive motivation in conditions of an unavoidable electrocutaneous stimulus is accompanied in mice by increases in the expression to the c-fos gene in the hippocampus and cerebral cortex. As reinforcement and learning progress and the animals become able to achieve a useful result – avoiding the electrocutaneous shock – expression of the c-fos gene in these brain structures decreases. The level of expression of the c-fos gene was found to be different in animals in which defensive behavior had different efficacies. Expression was higher in mice making large numbers of errors than in mice with few errors during acquisition of the defensive habit.