RGD Reference Report - Prior exposure to chronic stress and MDMA potentiates mesoaccumbens dopamine release mediated by the 5-HT(1B) receptor. - Rat Genome Database

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Prior exposure to chronic stress and MDMA potentiates mesoaccumbens dopamine release mediated by the 5-HT(1B) receptor.

Authors: Amato, JL  Bankson, MG  Yamamoto, BK 
Citation: Amato JL, etal., Neuropsychopharmacology. 2007 Apr;32(4):946-54. Epub 2006 Aug 2.
RGD ID: 1626459
Pubmed: (View Article at PubMed) PMID:16885935
DOI: Full-text: DOI:10.1038/sj.npp.1301174

(+) 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 x 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-HT(1B) 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-HT(1B) receptor in the VTA.

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Genes (Rattus norvegicus)
Htr1b  (5-hydroxytryptamine receptor 1B)


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