Attenuation of heroin reward in rats by disruption of the mesolimbic dopamine system.
The rewarding properties of systemically administered heroin were investigated with a conditioned place-preference paradigm. Reinforcing effects were observed with all doses of heroin tested (0.5, 1.0, 2.0 mg/kg) as indicated by a significant increase in preference for the place paired with drug injections. No similar change in preference was observed following saline injections. The rewarding effect of heroin (2 mg/kg) was attenuated by pretreatment with haloperidol (0.2 mg/kg), but haloperidol alone did not produce a place aversion. Lesions induced by 6-hydroxydopamine (6-OHDA) of the mesolimbic dopaminergic pathway at the level of the nucleus accumbens also attenuated the heroin-induced place preference. In contrast, depletion of central and peripheral noradrenaline induced by 6-OHDA had no significant effect on heroin-induced place preference. These data suggest an important role for the mesolimbic DA system in mediating the reinforcing effects of heroin.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D003932:Heroin / Q000494:pharmacology*; D006892:Hydroxydopamines / Q000494:pharmacology; D008032:Limbic System / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000502:physiology; D009714:Nucleus Accumbens / Q000502:physiology; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D012201:Reward
D006892:Hydroxydopamines; D003932:Heroin; D016627:Oxidopamine; D004298:Dopamine; D009638:Norepinephrine