Serotonergic Modulation Of Basolateral Amygdala Nucleus In The Extinction Of Reward-Driven Learning: The Role Of 5-Ht Bioavailability And 5-Ht1a Receptor

Serotonin (5-HT) neurotransmission has been associated with reward-related behaviour. Moreover, the seroto-nergic system modulates the basolateral amygdala (BLA), a structure involved in reward encoding , and reward prediction error. However, the role played by 5-HT on BLA during a reward-driven task has not been fully elucidated. In this paper, we investigated whether serotonergic modulation of the BLA is involved in reward-driven learning. To this end, we trained Long Evans rats in an operant conditioning task, and examined the ef-fects of fluoxetine treatment (a selective serotonin reuptake inhibitor, 10 mg/kg) in combination with BLA le-sions with NMDA (20 mg/mL) on extinction learning. We also investigated whether intra-BLA injection of the serotonergic 5-HT1A receptor agonist 8-OH DPAT, or antagonist WAY-100635, alters extinction performance. We found that fluoxetine treatment strongly accelerated extinction learning, while BLA lesions partially reverted this effect and slightly impaired consolidation of extinction. Stimulation and inhibition of 5-HT1A receptors in BLA induced opposite effects to those of fluoxetine, impairing or accelerating extinction performance, respectively. Our findings suggest that 5-HT modulates reward-driven learning, and 5-HT1A receptors located in the BLA are relevant for extinction.