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

After repeated intermittent exposure to psychostimulants, an increase in th e behavioral response to the drug is observed. The development of this sens itized response is greatly influenced by environmental cues. For example, w hen the pretreatments are administered in an environment distinct from the test, a sensitized response is often not observed. This finding has led som e investigators to suggest that sensitization is completely context depende nt. The present experiment established context-independent sensitization by administering pretreatments in an environment distinct from the test and m easured the effects of pretreatment on potency and/or efficacy of subsequen t cocaine administrations. Separate groups of rats received single or multi ple daily injections of cocaine (10.0 mg/kg) or the saline vehicle in the h ome cage during a 5-day pretreatment phase. Ninety-six hours following the last of the pretreatment injections the locomotor-activating effects of coc aine (0.0, 5.0, 10.0, or 20.0 mg/kg) were measured. For control rats, a sig nificant increase in motor activity was obtained following administration o f the 20.0 mg/kg dose. Rats that received the cocaine pretreatment became s ensitized to cocaine's motor activating effects. For these rats, cocaine pr etreatment produced a leftward shift in the dose-effect curve, consistent w ith an increased potency. The maximum locomotor response was not altered by pretreatment, suggesting that drug efficacy was not effected by preexposur e. Thus, context-independent sensitization to cocaine reflects an increased potency, but not efficacy, of the drug. (C) 1999 Elsevier Science Inc.