Serotonergic modulation of basolateral amygdala nucleus in the extinction of reward-driven learning: The role of 5-HT bioavailability and 5-HT1A receptor

Behav Brain Res. 2021 Apr 23:404:113161. doi: 10.1016/j.bbr.2021.113161. Epub 2021 Feb 8.

Abstract

Serotonin (5-HT) neurotransmission has been associated with reward-related behaviour. Moreover, the serotonergic 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 effects of fluoxetine treatment (a selective serotonin reuptake inhibitor, 10 mg/kg) in combination with BLA lesions 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.

Keywords: 5-HT(1A); Basolateral amygdala; Extinction; Fluoxetine; Operant conditioning; Serotonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Basolateral Nuclear Complex / drug effects*
  • Basolateral Nuclear Complex / metabolism
  • Basolateral Nuclear Complex / physiology
  • Biological Availability
  • Conditioning, Operant / drug effects*
  • Conditioning, Operant / physiology
  • Extinction, Psychological / drug effects*
  • Extinction, Psychological / physiology
  • Fluoxetine / pharmacology
  • Male
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Rats
  • Rats, Long-Evans
  • Receptor, Serotonin, 5-HT1A / drug effects*
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Receptor, Serotonin, 5-HT1A / physiology
  • Reward
  • Serotonin / pharmacokinetics
  • Serotonin / pharmacology*
  • Serotonin 5-HT1 Receptor Agonists / pharmacology
  • Serotonin 5-HT1 Receptor Antagonists / pharmacology

Substances

  • Piperazines
  • Pyridines
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • Fluoxetine
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • 8-Hydroxy-2-(di-n-propylamino)tetralin