title: Motivational state determines the functional role of the mesolimbic dopamine system in the mediation of opiate reward processes.
abstract: We have previously reported that mesolimbic dopamine (DA) substrates are critically involved in the rewarding effects of opiates only during states of opiate-dependence and withdrawal. However, in previously drug-naive animals, opiate reward is mediated through a DA-independent neural system. In the present study, we report that bilateral microinjections of a DA receptor antagonist, alpha-flupenthixol (0.3-3 microg/0.5 microl) into the nucleus accumbens (NAc), blocks morphine reward (10 mg/kg, i.p.) in opiate-withdrawn animals, but not in opiate-naive animals, suggesting that accumbal dopamine receptors are required for opiate reward signaling in drug-deprived motivational states. Next, the role of dopamine was examined in the development of opiate dependence and somatic withdrawal, and expression of withdrawal aversions. Pretreatment with alpha-flupenthixol (0.8 mg/kg, i.p.) before morphine injections during the development of opiate dependence did not effect expression of withdrawal aversions or the expression of somatic withdrawal. We have previously reported that pretreatment with a dopamine receptor antagonist, alpha-flupenthixol, blocks the aversive effects of opiate withdrawal. We now report that pretreatment with a direct dopamine receptor agonist, apomorphine (1.0-5.0 mg/kg, i.p.) before conditioning in a state of withdrawal, also blocks the aversive effects of opiate withdrawal. We propose that the aversive motivational effects of opiate withdrawal may be mediated by a specific dopaminergic neuronal signal.
authors.affiliation: Department of Anatomy and Cell Biology, Neurobiology Research Group, University of Toronto, Medical Sciences Building, Toronto, Ont., Canada. stevelaviolette@hotmail.com
authors.forename: Steven R
authors.initials: SR
authors.lastname: Laviolette
authors.forename: Karim
authors.initials: K
authors.lastname: Nader
authors.forename: Derek
authors.initials: D
authors.lastname: van der Kooy
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D005475:Flupenthixol / Q000008:administration & dosage / Q000494:pharmacology; D008032:Limbic System / Q000033:anatomy & histology / Q000502:physiology*; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000009:adverse effects; D009021:Morphine Dependence / Q000523:psychology; D009042:Motivation; D009294:Narcotics / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D013375:Substance Withdrawal Syndrome / Q000523:psychology
chemical_list: D014150:Antipsychotic Agents; D009294:Narcotics; D009020:Morphine; D005475:Flupenthixol; D018021:Lithium Chloride; D004298:Dopamine