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The effects of bilateral hippocampal lesions and systemic elevation of ACTH were compared using the classically conditioned rabbit nictitating membrane response. Animals with hippocampal lesions and unoperated animals that received ACTH (5 I.U./kg) exhibited a facilitated rate of acquisition and decreased conditioned response onset latency relative to normal control groups or animals with cortical lesions. The administration of ACTH did not alter performance in animals with hippocampal damage, indicating that the effects of these treatments are not additive. The performance of a second group of animals that was treated with a smaller dosage of ACTH (2.5 I.U./kg) was no different from that of any other group, suggesting a dose-dependent effect of the hormone. The selective replication of hippocampal deficits ascribed to a loss of response modulation suggests that ACTH may influence learning by stimulating hippocampal neurons.

Neural and endocrine effects on classical conditioning: A comparison of ACTH and hippocampectomy