Changes in dopaminergic neurotransmission do not alter somatic or motivational opiate withdrawal-induced symptoms in rats.
Opiate withdrawal has been correlated with decreased extracellular dopamine (DA) levels in the nucleus accumbens (NAC) of morphine-dependent rats. The authors tested the hypothesis that DA transmission plays a critical role in the induction of motivational and somatic withdrawal symptoms. First, the authors used a 6-hydroxydopamine-induced lesion of the NAC to chronically disrupt mesolimbic DA transmission. Second, global DA neurotransmission was acutely stimulated by the nonselective DA agonist (apomorphine) or inhibited by nonselective DA antagonists (droperidol or flupentixol). Morphine-dependent rats bearing 6-hydroxydopamine-induced lesions displayed naloxone-precipitated motivational and somatic withdrawal symptoms similar to those of sham-lesioned rats. Administration of apomorphine did not reduce naloxone-induced opiate withdrawal. Moreover, in total absence of naloxone, DA antagonists did not precipitate either conditioned place aversion or somatic abstinence signs in dependent rats. Taken together, these findings suggested that DA transmission is not critical for the induction of opiate withdrawal syndrome.
Centre Nacional de la Recherche Scientifique, Unite Mixte de Recherche (CNRS-UMR) 5541, Lab de Neuropsychobiologie de Desadaptations, Université Bordeaux II, Bordeaux, France. scaille@scripps.edu
Stéphanie
S
Caillé
Marta
M
Rodriguez-Arias
Jose
J
Minarro
Emilio F
EF
Espejo
Martine
M
Cador
Luis
L
Stinus
D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D009042:Motivation; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D009294:Narcotics; D011954:Receptors, Dopamine; D009270:Naloxone