Opiate reward: sites and substrates.

Opiates appear to have rewarding actions at more than one locus in the brain. Studies of the effects of dopaminergic lesions and dopamine receptor blockade indicate that intravenous heroin self-administration depends importantly on a dopaminergic substrate. Mapping of effective injection sites for morphine-conditioned place preference establishes one site of rewarding action near the dopamine cell bodies of the ventral tegmental area (VTA). Studies of the complex interactions of opiates, neuroleptics, and brain stimulation reward confirm that reward-related VTA opioid actions are dopamine-dependent. Opioid injections into the nucleus accumbens (NAS) also facilitate brain stimulation reward and serve as rewards in their own right, though these actions have not yet been localized by identification of negative sites in surrounding regions. The relation of this putative reward site to the dopamine system is not yet clear. Suggestions that the lateral hypothalamus or periaqueductal gray contain opioid reward sites remain to be confirmed. While opioid injections into these sites can be rewarding, these rewarding effects have not been localized to these sites, and opiate injections into each of these areas are reported not to facilitate brain stimulation reward. Intravenous heroin self-administration is not disrupted by kainic acid lesions of the bed nucleus of the lateral hypothalamus. Thus only the VTA and the NAS are firmly established as sites of opiate rewarding actions. Recent reports suggest that the kappa-opioid dynorphin may also have central rewarding actions and central and peripheral aversive actions; the CA3 region of the hippocampus is a possible site of the rewarding action.