Neural substrates of opiate reinforcement

1. 1. A major component of opiate reward is derived from a drug action in the ventral tegmental area: (a) rats quickly learn to self-administer morphine directly into the ventral tegmentum, (b) intracranial self-administration into other brain sites is not quickly learned, and (c) narcotic antagonist microinjections into the ventral tegmentum attenuate reward from intravenous heroin infusions. 2. 2. At least one component of opiate reward is dependent on a dopaminergic system: (a) electrophysiological and neurochemical indices suggest that opiates activate ventral tegmental dopaminergic neurons, (b) ventral tegmental opiate infusions are behaviorally activating producing contralateral rotation that is blocked by neuroleptics, (c) reward from heroin is blocked by neuroleptics, and (d) reward from heroin is attenuated by dopamine-depleting lesions of the ventral tegmental system. 3. 3. Brain sites involved in the production of physical dependence on opiates are anatomically distinct from those initiating the acutely rewarding action of opiates. 4. 4. It is theoretically viable that opiates derive their reinforcing impact from a combination of positive and negative reinforcement processes: (a) the neural substrate for the positive reinforcing action probably involves a ventral tegmental dopamine system important in appetitive motivation, and (b) the neural substrate for the negative reinforcing action may involve a periventricular gray system that is independent of the system which mediates the acutely rewarding property of opiates.