Unraveling the role of serotonin in reward-directed learning

FRICK LUCIANA ROMINA; RAPANELLI M; ZANUTTO BS

Washington

Congreso; Annual Meeting of the Society for Neuroscience; 2011

SfN - Society for Neuroscience

The Ventral Tegmental Area (VTA) and the medial Prefrontal Cortex (mPFC) are considered the most important brain structures that control reward-dependent behaviors. The VTA is known to project dopaminergic axons to the mPFC. In addition, the mPFC is innervated by serotonergic axons and express serotonin (5-HT) receptors. Although the role of dopamine (DA) in goal-directed behaviors is well studied, the participation of 5-HT remains controversial. Using the appetitive operant conditioning task in rats, we found that the pharmacological blockade of DA degradation with Entacapone in the mPFC improved the performance of the animals, i.e. higher number of responses and lower latency time to respond. In addition, depletion of DA with recombinant cathechol-O-methyl transferase inhibitor (COMT) resulted in the opposite effect. Instead, 5-Hydroxytryptophan (5-HTP, a chemical precursor of 5-HT), did not alter the number of responses but significantly increased the latency time. The pharmacological blockade of the 5-HT transporter (SERT) with the reuptake inhibitor Fluoxetine not only delayed the time to respond, but also reduced the number of correct responses in successive training sessions. Therefore, our results indicate that whereas DA is a ?positive codifier? of the reward, the 5-HT may be a ?negative codifier? of the same. This is in accordance to the hypothesis of the 5-HT system of the dorsal raphe nucleus (DR) as an opponent system to DA in conditioning tasks. We also propose that 5-HT may be involved in representing and therefore learning the negative prediction errors.