Issues in the pharmacological modification of cocaine conditioning: evidence that the stimulus properties of drugs can interact with contextual cues to activate or inactivate cocaine conditioned stimuli

Cocaine conditioned stimuli are capable of eliciting cocaine craving in ind ividuals with a history of cocaine use. As a consequence, there have been a number of attempts using animal models to identify pharmacological treatme nts which can attenuate cocaine conditioned effects. The emphasis in these studies has been to employ drug doses which do not have response effects th at could directly alter the conditioned drug response. A drug treatment may not have a response effect but still have drug stimulus effects which coul d interact with and modify the cocaine conditioned stimulus. In order to ex perimentally investigate this important issue, two experiments are reported . In one experiment, rats were co-administered 0.1 mg/kg MK-801 either with cocaine (10 mg/kg) or with saline; in the other experiment 3.0 mg/kg buspi rone was co-administered with either cocaine (10 mg/kg) or with saline. The MK-801 and buspirone treatments did not affect spontaneous activity levels or alter the unconditioned cocaine stimulant effect. In tests for conditio ning, however, the effects of buspirone and MK-801 depended upon their asso ciation with cocaine. If MK-801 and buspirone had no association with cocai ne then these drugs inactivated the cocaine conditioned stimulant response. If MK-801 and buspirone had been co-administered with cocaine, then, in sa line conditioning tests, no cocaine conditioning was observed. If the condi tioning tests were conducted following MK-801 or buspirone treatment, howev er, cocaine conditioning was elicited. Altogether, these studies demonstrat e that the stimulus properties of drugs can interact with contextual stimul i to inactivate or activate cocaine conditioned stimuli. In the search for drugs which may prevent cocaine craving, therefore, the stimulus properties of drugs provide an important mechanism for the modification of cocaine co nditioned stimuli. (C) 1999 Elsevier Science B.V. All rights reserved.