Differential mechanisms in the acquisition and expression of heroin-induced place preference.
These experiments examined the neurochemical mechanisms involved in the development and expression of place conditioning produced by heroin. Conditioned place preferences (CPP) lasting up to 8 weeks were obtained with doses of 50-1000 micrograms/kg heroin, using a regimen shown not to produce physical dependence. Naloxone pretreatment (50 micrograms/kg) during conditioning prevented the acquisition of heroin-induced CPP, but when given only on the test day, naloxone (50 or 1000 micrograms/kg) did not prevent the expression of heroin CPP. Clonidine disrupted the establishment of heroin CPP at 20 micrograms/kg, but disrupted its expression only at debilitating doses (100 and 200 micrograms/kg). Pimozide attenuated the acquisition (100 micrograms/kg) and expression (250 micrograms/kg) of heroin CPP. Together, these results support a role for opioid and catecholamine systems in the acquisition of heroin reinforcement, but they suggest that once heroin CPP is established, its expression in opiate-free subjects is not opiate receptor mediated and is relatively refractory to pharmacological treatments which disrupt acquisition. The data challenge the notion that the conditioned effects of opiates in drug-free animals are related to the release of endogenous opioids, and they also may help to explain why naloxone and clonidine are ineffective in the treatment of opiate addiction.
Hand
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Laboratoire de Psychobiologie des Comportements INSERM U-259, Bordeaux, France.
Stinus
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Le Moal
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D000818:Animals; D002755:Choice Behavior / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D003932:Heroin / Q000494:pharmacology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D010868:Pimozide; D009270:Naloxone; D003932:Heroin; D003000:Clonidine