Context-independent sensitization to the locomotor-activating effects of cocaine

After repeated intermittent exposure to psychostimulants, an increase in the behavioral response to the drug is observed. The development of this sensitized response is greatly influenced by environmental cues. For example, when the pretreatments are administered in an environment distinct from the test, a sensitized response is often not observed. This finding has led some investigators to suggest that sensitization is completely context dependent. The present experiment established context-independent sensitization by administering pretreatments in an environment distinct from the test and measured the effects of pretreatment on potency and/or efficacy of subsequent cocaine administrations. Separate groups of rats received single or multiple daily injections of cocaine (10.0 mg/kg) or the saline vehicle in the home cage during a 5-day pretreatment phase. Ninety-six hours following the last of the pretreatment injections the locomotor-activating effects of cocaine (0.0, 5.0, 10.0, or 20.0 mg/kg) were measured. For control rats, a significant increase in motor activity was obtained following administration of the 20.0 mg/kg dose. Rats that received the cocaine pretreatment became sensitized to cocaine's motor activating effects. For these rats, cocaine pretreatment produced a leftward shift in the dose-effect curve, consistent with an increased potency. The maximum locomotor response was not altered by pretreatment, suggesting that drug efficacy was not effected by preexposure. Thus, context-independent sensitization to cocaine reflects an increased potency, but not efficacy, of the drug. (C) 1999 Elsevier Science Inc.