1. 1. Humans and laboratory animals given access to opiate and stimulant drugs frequently become compulsive users of these drugs, and often, in spite of prolonged periods of abstinence, persist in drug-seeking behavior and relapse to drug-taking. Evidence suggests that such drugs act on positive appetitive systems of the brain to maintain drugtaking and that, in the absence of drugs, stimuli previously associated with the drug state might acquire the ability to arouse motivational states similar to those activated by the drugs themselves.
2. 2. In rats previously trained to self-administer cocaine or heroin intravenously, noncontingent ‘priming’ intravenous infusions of cocaine or heroin lead to reinstatement of drugtaking behavior. Priming infusions of pharmacologically related drugs and drugs with similar stimulus properties also reinstate responding.
3. 3. Application of morphine to the cell body region of dopaminergic neurons of the ventral tegmental area (VTA), a site known to support morphine self-administration, reinstates both heroin and cocaine self-administration behavior. Reinstatement is blocked by pretreatment with naltrexone. Morphine applied to several other brain areas rich in opiate receptors does not reinstate the behavior.
4. 4. Application of morphine to the VTA, a site known to support conditioned place preferences as well as self-administration, causes increased locomotion that is naloxone reversible. This locomotor activity shows sensitization upon repeated administration; an effect that is specific to the environment in which morphine is administered. Conditioned increases in activity are observed in the same environment. Neither conditioning nor sensitization develops when animals are pretreated with pimozide.
5. 5. These findings support the view that, opiates and stimulants are administered because of their effects on positive appetitive systems of the brain and that, through conditioning, stimulus events that are associated with these positive appetitive actions of opiates and stimulants acquire the ability to elicit neural states that mimic aspects of those elicited by the drugs themselves. The arousal of these states may act to reinstate (facilitate relapse) and to maintain drug-taking behavior. This positive incentive account of compulsive drug-taking and relapse differs from the ‘drive-reduction’ view that continued drug use depends primarily on efforts to reduce or avoid symptoms of withdrawal, and that conditioned stimuli associated with drugs can initiate and maintain drug-taking behavior through the elicitation of withdrawal-like, drug-opposing, conditioned responses.
Author Keywords: conditioning; opiates; reinstatement; relapse to drug-taking; sensitization; stimulants
