Brain mechanisms of drug-induced reinforcement.

The results of the experiments described above suggest that although the abused psychomotor stimulants and opioids have independent actions that contribute to their reinforcing effects, there are common neuronal substrates for some of their rewarding effects. Additionally there is considerable evidence implicating dopamine systems in these rewarding effects. The neuronal systems involved in these pharmacological actions may be similar to those involved in the rewarding effects of electrical stimulation to the brain. Although both classes of compounds cause euphoria in humans and are reinforcing in animals, the opioids are also central nervous system depressant drugs. These depressant properties influence the subjective effects in humans and possibly the nature of the rewarding effect in animals. Experiments using the 2-deoxyglucose procedure indicate that BSR to either the ventral tegmental area or the medial forebrain bundle results in functional activation throughout the mesocorticolimbic system. The major effects are found in the nucleus accumbens, olfactory tubercle, and the medial prefrontal cortex. Cocaine produces increases in metabolic rates similar in distribution to BSR. Morphine, however, only causes significant increases in functional activity in the olfactory tubercle. Further, only in this brain site did the combination of BSR plus morphine or cocaine cause increases in functional activity over that of stimulation alone. These findings suggest that the olfactory tubercle plays a major role in the pharmacological actions of both the psychomotor stimulants and the opioids as well the rewarding effects of electrical stimulation of the brain.