Serotonin 5-HT(2C) agonists selectively inhibit morphine-induced dopamine efflux in the nucleus accumbens

David L. Willins*, Herbert Y. Meltzer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

In vivo microdialysis was used to compare the effects of serotonergic drugs on morphine- and cocaine-induced increases in extracellular dopamine (DA) concentrations in the rat nucleus accumbens (NAc). Systemic administration of the 5-HT(2A/2C) receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (2.5 mg/kg, s.c.) prevented the increase in extracellular DA in the NAc produced by morphine (5 mg/kg, i.p.). In contrast, this dose of DOI had no effect on the ability of cocaine (10 mg/kg, i.p.) to increase extracellular DA concentrations in the NAc. A preferential 5-HT(2C) receptor agonist, 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212, 5 mg/kg, s.c.) also inhibited morphine-induced increases in extracellular DA concentrations in the NAc. Pretreatment of rats with the selective 5-HT(2A) antagonist, amperozide, had no effect on morphine-induced elevation of NAc DA concentrations. In order to determine if inhibition of the firing of 5-HT neurons contributes to the serotonin agonist-mediated inhibition of morphine-induced accumbens DA release, rats were pretreated with the 5-HT(1A) agonist, 8-OHDPAT. At a dose of 100 μg/kg (s.c.), 8-OHDPAT did not interfere with morphine's ability to increase DA concentrations in the NAc. These results suggest that the activation of 5-HT(2C) receptors selectively inhibits morphine-induced DA release in the NAc in a manner which is independent of the inhibition of 5-HT neurons.

Original languageEnglish (US)
Pages (from-to)291-299
Number of pages9
JournalBrain research
Volume781
Issue number1-2
DOIs
StatePublished - Jan 19 1998

Keywords

  • Cocaine
  • Dopamine
  • Microdialysis
  • Morphine
  • Nucleus accumbens
  • Serotonin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Serotonin 5-HT(2C) agonists selectively inhibit morphine-induced dopamine efflux in the nucleus accumbens'. Together they form a unique fingerprint.

Cite this