Serotonin 5-HT2C agonists selectively inhibit morphine-induced dopamine efflux in the nucleus accumbens

Brain Res. 1998 Jan 19;781(1-2):291-9. doi: 10.1016/s0006-8993(97)01267-5.


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-HT2A/2C 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 5-HT2C selective 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-HT2A 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-HT1A agonist, 8-OHDPAT. At a dose of 100 microg/kg (sc), 8-OHDPAT did not interfere with morphine's ability to increase DA concentrations in the NAc. These results suggest that the activation of 5-HT2C receptors selectively inhibits morphine-induced DA release in the NAc in a manner which is independent of the inhibition of 5-HT neurons.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Amphetamines / pharmacology
  • Animals
  • Cocaine / pharmacology
  • Dopamine / metabolism*
  • Dopamine Uptake Inhibitors / pharmacology
  • Male
  • Microdialysis
  • Morphine / antagonists & inhibitors*
  • Narcotic Antagonists / pharmacology*
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Piperazines / pharmacology
  • Pyrazines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology*


  • Amphetamines
  • Dopamine Uptake Inhibitors
  • Narcotic Antagonists
  • Piperazines
  • Pyrazines
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • amperozide
  • 6-chloro-2-(1-piperazinyl)pyrazine
  • Morphine
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Cocaine
  • 4-iodo-2,5-dimethoxyphenylisopropylamine
  • Dopamine