Modification of 8-OH-DPAT effects on learning by manipulation of the assay conditions

A role for the 5-HT_1A receptor in learning and memory has been suggested by diverse evidence. The present paper deals with the acute effect of 8-OH-DPAT (a 5-HT_1A agonist) administered to rats before or after training in an autoshaped lever-press response (a model of associative learning). The results show that 8-OH-DPAT improved consolidation of the conditioned response (CR) when injected post-training, but impaired it with pretraining administration. Both effects were time-dependent. When the compound was administered pre- or post-training to free-feeding or prefeeding animals, they did not learn the CR. When it was administered to retrained food-deprived animals, the compound was also inactive. However, with retrained animals on a free-feeding schedule, pre- or post-training administration of 8-OH-DPAT enhanced retrieval in a dose-dependent fashion. Pretraining administration of 8-OH-DPAT impaired food intake and exploration, and therefore learning. The present results strongly suggest a role of 5-HT_1A receptors in the consolidation and retrieval of learning. Such improvement is independent of food intake.