Strategies for studying the neurochemical substrates of drug reinforcement in rodents.

Results from three different experimental paradigms for studying drug reinforcement are reviewed. Rate-increasing effects of amphetamine on intracranial self-stimulation are abolished by lesions to ascending dopamine neurons. Rate-increasing effects of intracranial microinjection of opioids on self-stimulation are localized to the vicinity of dopamine cell bodies in the ventral tegmentum. Conditioned reinforcement produced with intracranial microinjection of opioids into the ventral tegmental area is blocked by the dopamine antagonist haloperidol and lesions to ascending dopamine pathways. Intravenous self-administration of cocaine is blocked by intracerebral microinjection of spiroperidol into the nucleus accumbens but not into the caudate nucleus. Ascending dopamine neurons appear to mediate some of the reinforcing properties of both psychomotor stimulants and opioids.