Brain substrates for reinforcement and drug self-administration

• 1.

  1. Animals will work for stimulation of some parts of their own brains; this suggests that the brain has specialized circuitry for mediation of reward.

• 2.

  2. Current evidence identifies two links in such circuitry: a myelinated, descending, medial forebrain bundle link and an ascending, dopaminergic, medial forebrain bundle link. The myelinated link makes probable synaptic contact with the dopaminergic cells of the ventral tegmental area and substantia nigra. These dopaminergic cells may receive other myelinated and reward-relevant afferents as well, particularly from the brainstem.

• 3.

  3. Psychomotor stimulants facilitate intracranial self-stimulation by acting at terminals of the dopaminergic link, particularly in nucleus accumbens. Opiates facilitate self-stimulation by acting at the dopamine cell bodies in the ventral tegmentum. Facilitation of self-stimulation by other drugs of abuse has not been localized to a site of action.

• 4.

  4. Psychomotor stimulants have rewarding actions of their own in nucleus accumbens. Opiates have rewarding actions at the dopaminergic cell body region of the ventral tegmentum. The sites of rewarding action have not been determined for other drugs of abuse.

• 5.

  5. The substrate mediating rewarding actions of opiates and psychomotor stimulants also mediates the rewarding action of more natural rewards like food and water. The fact that some drugs of abuse can come to dominate behavior in relation to more natural rewards may stem from the more direct central actions of drugs on the reward substrate. The fact that the rewarding effects of food, water, opiates, and psychomotor stimulants feel subjectively dissimilar may simply reflect the fact that while a common rewarding action is shared by these agents, many other effects which are subjectively experienced differ between agents and obscure awareness of a common dimension of all positive rewards.