Heroin self-administration: effects of antagonist treatment in lateral hypothalamus

The involvement of the lateral hypothalamus and medial prefrontal cortex in mediating heroin self-administration was examined by means of intracranial microinjections of the quaternary opiate antagonist methyl naltrexone over a dose range of 0-3.0 micrograms. In animals trained to respond on a continuous reinforcement schedule for intravenous heroin (0.03 mg/kg/infusion), microinfusions of antagonist into the lateral hypothalamus prior to a self-administration session produced significant dose-related increases in responding on the drug manipulandum, similar to increases in responding observed after treatment with naltrexone systemically. Microinfusions of quaternary antagonist into the medial prefrontal cortex over the same dose range effective in the lateral hypothalamus did not produce response increases. These data suggest that opiate action in the lateral hypothalamus, but not in the medial prefrontal cortex, is salient in maintenance of intravenous self-administration.