One-trial cocaine-induced behavioral sensitization in preweanling rats: role of contextual stimuli

Using a one-trial procedure, preweanling rats exhibit robust sensitization regardless of whether drug pretreatment and testing occur in the same or different environments. The purpose of the present study was to determine whether one-trial context-specific and context-independent sensitization of preweanling rats could be dissociated by varying the pretreatment dose of cocaine, by varying the pretreatment drug, or by minimizing interoceptive cues. In Experiments 1a and 1b, rats were pretreated with a broad dose range of cocaine (0-40 mg/kg) before placement in a novel activity chamber or the home cage. In Experiment 2, rats were pretreated with a locomotor-enhancing drug (e.g., methylphenidate, U50,488, or MK-801) before placement in a novel activity or anesthesia chamber. In Experiment 3, rats were anesthetized with isoflurane before cocaine administration to minimize the effects of interoceptive and injection cues. In all experiments, rats were challenged with cocaine on the test day (24 hr later), with locomotion being measured in activity chambers. Results showed that (a) the pretreatment dose of cocaine (10-40 mg/kg) did not differentially affect context-specific and context-independent sensitization; (b) cross-sensitization between methylphenidate and cocaine was observed in the context-specific condition, but not when using a context-independent procedure; and (c) sensitization was evident if injection and interoceptive cues were minimized. One possibility is that associative processes do not modulate the one-trial sensitization of preweanling rats. Alternatively, "unitization" may cause preweanling rats to treat the different environments as equivalent, thus permitting robust sensitization even when drug pretreatment and testing occur in different environments.