LACK OF EVIDENCE FOR CONTEXT-DEPENDENT COCAINE-INDUCED SENSITIZATION IN HUMANS - PRELIMINARY STUDIES

Cocaine-induced behavioral sensitization is the well-documented phenom enon where repeated doses of cocaine elicit increasingly greater effec ts on motoric activity in rats. Some observations suggest that behavio ral sensitization may provide a model for understanding the mechanisms of drug-craving elicited by environmental triggers or cues. The proce ss of fully validating such an animal model for its ability to detect effective anticraving medicines is a difficult and long-term undertaki ng. As a first step in that direction, we decided to determine if coca ine can produce conditioned behavioral sensitization in humans using a paradigm fairly similar to that used for rodents. Because humans do n ot react to cocaine with the pronounced motor activation observed in r odents, we measured a variety of end points, including blood pressure (BP), heart rate (HR), respiratory rate, pupil diameter, hormones (pro lactin and cortisol), and subjective responses using the questionnaire for drug-related feelings (QDRF) and the EEG. To mimic the home and t est cages used in rodent studies, two rooms were used: a small test ch amber and a regular room with a window and furnishings. On day 1 each subject received a drug infusion (either saline or 40 mg cocaine IV) i n both locations. On day 2, all subjects received an infusion (saline or 25 mg cocaine IV) in the test chamber. All drug infusions were cond ucted double blind. The paired group received cocaine on both days in the test chamber. The unpaired group received cocaine in regular room on day 1, and cocaine in the test chamber on day 2. A control-1 group received saline at both locations on day 1, and cocaine on day 2 in th e test chamber. A control-2 group [4] received cocaine in the test cha mber on day 1 and saline in the test chamber on day 2. Conditioned-sen sitization was not observed. However, conditioned tolerance was observ ed for cocaine-induced changes in plasma prolactin levels and diastoli c blood pressure. Because rodent studies use cocaine-naive subjects an d this study used cocaine-experienced subjects, these data suggest tha t prior experience with cocaine may alter it ability to produce sensit ization. Viewed collectively, the present investigation suggests cauti on in the design of both human and animal studies.