Prior exposure to chronic stress and MDMA potentiates mesoaccumbens dopamine release mediated by the 5-HT(1B) receptor.
(+) 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.
Amato
Jennifer L
JL
Laboratory of Neurochemistry, Department of Pharmacology, Boston University School of Medicine, Boston, MA 02118, USA.
Bankson
Michael G
MG
Yamamoto
Bryan K
BK
D000704:Analysis of Variance; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry / Q000379:methods; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology*; D013312:Stress, Physiological / Q000378:metabolism* / Q000473:pathology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
D044302:Receptor, Serotonin, 5-HT1B; D018490:Serotonin Agents; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine