Prior exposure to chronic stress and MDMA potentiates mesoaccumbens dopamine release mediated by the 5-HT1B receptor

Jennifer L. Amato, Michael G. Bankson, Bryan K. Yamamoto

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

(+) 3,4,-Methylenedioxymethamphetamine (MDMA) is an abused drug that acutely releases serotonin (5-HT) and dopamine (DA) but produces long-term damage to 5-HT terminals. MDMA-induced DA release has been shown to be dampened by 5-HT. Although stress also activates the mesolimbic DA pathway, it is unknown if chronic stress after exposure to neurotoxic doses of MDMA will augment MDMA-induced DA release in the nucleus accumbens shell (NAcc(sh)). Rats were pretreated with MDMA (10 mg/kg × 4, intraperitoneal (i.p.)). After 7 days, rats were subjected to 10 days of chronic unpredictable stress. DA release in the NAcc(sh) and 5-HT in the ventral tegmental area (VTA) were measured after a challenge injection of MDMA (5 mg/kg, i.p.). The combination of pretreatment with MDMA+stress decreased basal concentrations of 5-HT in the VTA and DA in the NAcc(sh) and enhanced MDMA-stimulated DA release in the NAcc(sh). Pretreatment with MDMA or stress alone blunted MDMA-induced 5-HT release in the VTA. The augmentation of MDMA-induced DA release in rats pretreated with MDMA+chronic stress was attenuated by perfusion of the 5-HT1B antagonist, GR127935 into the VTA before the MDMA challenge injection. These results suggest that prior exposure to both MDMA and stress can produce a long-term augmentation in mesolimbic DA transmission and enhanced drug abuse vulnerability that is mediated, in part, by the 5-HT1B receptor in the VTA.

Original languageEnglish (US)
Pages (from-to)946-954
Number of pages9
JournalNeuropsychopharmacology
Volume32
Issue number4
DOIs
StatePublished - Mar 7 2007
Externally publishedYes

Keywords

  • Chronic unpredictable stress
  • Dopamine
  • MDMA
  • Nucleus accumbens shell
  • Serotonin
  • Ventral tegmental area

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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