Serotonin involvement in operant learning: a role for 5-HT1A and 5-HT3 receptors in the Hippocampus and the medial Prefrontal Cortex

FRICK LUCIANA ROMINA; HOCHT CHRISTIAN; BERNARDEZ MICAELA; ZANUTTO SILVANO; RAPANELLI MAXIMILIANO

New Orleans, LA, USA

Congreso; Reunion Anual de la Society for Neuroscience; 2012

Society for Neuroscience.

Here we studied the involvement of serotonin (5-HT) in an operant conditioning task in Long Evans rats, the role of the medial Prefrontal Cortex (mPFC) and the Hippocampus (Hipp), and the participation of 5-HT1A and 5-HT3 receptors. 5-HT inhibits pyramidal neurons in the mPFC and principal cells in the Hipp through 5-HT3 receptors present in GABAergic interneurons. Thus, the antagonist Ondansetron (2 mg/kg) was administered prior each training session. Ondansetron significantly reduced the number of responses in the second and third session, as well as the latency times to respond in the third session. Besides, the inhibitory receptor 5-HT1A is expressed in pyramidal neurons of the mPFC and the Hipp as well as in granular cells from the dentate gyrus. Therefore, the partial agonist of this receptor Buspirone was also administered. Buspirone (10 mg/kg) reduced the percentage of responses only in the first session but increased the latency time to respond until the last session of training. Then, total 5-HT levels were determined in the mPFC and the Hipp by HPLC. Partially trained animals (50-65% of correct responses) had increased levels of 5-HT in the mPFC. However after reaching a 100% of correct responses, 5-HT levels returned to basal values. Instead, no changes were found in 5-HT levels in the Hipp of both groups of animals. Interestingly, 5-HT levels in the mPFC were inversely correlated with the number of responses (Spearman’s p<0.01), whereas they were directly correlated with latency times (Spearman’s p<0.05). Taken together, these results suggest that the serotonergic circuit comprising the mPFC is involved in the learning of a reward-dependent task.