Conditioned and unconditioned drug effects in relapse to opiate and stimulant drug self-adminstration

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 drug-taking 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. In rats previously trained to self-administer cocaine or heroin intravenously, noncontingent 'priming' intravenous infusions of cocaine or heroin lead to reinstatement of drug-taking behavior. Priming infusions of pharmacologically related drugs and drugs with similar stimulus properties also reinstate responding. 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. 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.(ABSTRACT TRUNCATED AT 250 WORDS)