Neuroleptics block high- but not low-dose heroin place preferences: further evidence for a two-system model of motivation.
The researchers studied whether 2 separate motivational systems in the brain underlie the rewarding effects of morphine. The brainstem tegmental pedunculopontine nucleus (TPP) is involved in mediating the motivational effects of opiates in nondeprived (drug-naive) rats, whereas dopamine transmission is necessary in mediating the motivational effects of opiates in deprived rats (opiate withdrawal). The results show that heroin's motivational properties obey the same boundary between a nondeprived and a deprived motivational state. Bilateral ibotenic acid lesions of the TPP blocked the acquisition of a place preference for an environment paired with 0.05 mg/kg heroin (a dose that induces no withdrawal aversion) but had no effect on place preference for an environment paired with 0.5 mg/kg heroin (a dose that does induce withdrawal aversion). Dopamine antagonist pretreatment produced the opposite pattern of results.
Nader
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Department of Anatomy and Cell Biology, University of Toronto, Ontario, Canada.
Bechara
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Roberts
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van der Kooy
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D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D001931:Brain Mapping; D001933:Brain Stem / Q000187:drug effects* / Q000503:physiopathology; D003214:Conditioning, Classical / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005475:Flupenthixol / Q000494:pharmacology; D003932:Heroin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006556:Heroin Dependence / Q000503:physiopathology; D008297:Male; D009042:Motivation; D010868:Pimozide / Q000494:pharmacology; D011292:Premedication; D051381:Rats; D017208:Rats, Wistar; D012931:Social Environment; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects
D014150:Antipsychotic Agents; D010868:Pimozide; D003932:Heroin; D005475:Flupenthixol; D004298:Dopamine