Intermittent access cocaine self-administration produces psychomotor sensitization: effects of withdrawal, sex and cross-sensitization.

Abstract

With repeated administration, the psychomotor activating effects of drugs such as cocaine or amphetamine can change in very different ways-showing sensitization or tolerance-depending on whether they are administered more or less intermittently. This behavioral plasticity is thought to reflect, at least in part, changes in dopamine (DA) neurotransmission, and therefore, may provide insights into the development of substance use disorders. Indeed, the most widely used preclinical model of cocaine addiction, which involves Long Access (LgA) self-administration procedures, is reported to produce tolerance to cocaine's psychomotor activating effects and effects on DA activity. In contrast, Intermittent Access (IntA) cocaine self-administration is more effective than LgA in producing addiction-like behavior, but sensitizes DA neurotransmission. There is, however, very little information concerning the effects of IntA experience on the psychomotor activating effects of cocaine. The objective of this study was to determine whether IntA experience produces psychomotor sensitization with similar characteristics to that produced by the intermittent, noncontingent administration of cocaine. IntA to cocaine did indeed produce psychomotor sensitization that (1) was greater after a long (30days) vs. short (1day) period of withdrawal, (2) was greater in females than males, and (3) resulted in cross-sensitization to another psychomotor stimulant drug, amphetamine. The tolerance sometimes associated with LgA cocaine self-administration has been cited in support of the idea that, in addiction, drug-seeking and drug-taking is motivated to overcome a DA deficiency and associated anhedonia. In contrast, the neurobehavioral sensitization associated with IntA cocaine self-administration favors an incentive-sensitization view.