Importance of environmental context for one- and three-trial cocaine-induced behavioral sensitization in preweanling rats

Abstract

Preweanling rats, unlike adults, exhibit context-independent behavioral sensitization after a single pretreatment injection of cocaine. The purpose of this study was to examine environmental factors modulating one- and three-trial sensitization in preweanling rats. For preweanling rats, drug pretreatments occurred on postnatal day (PD) 17-PD 19 (experiment 1) or PD 19 (experiment 2). One set of rats was injected with cocaine (30 mg/kg) and placed in anesthesia ("small"), operant conditioning ("large"), or activity chambers for 30 min. Rats were returned to the home cage and injected with saline. Additional groups of rats were injected with saline and placed in small, large, or activity chambers for 30 min and then injected with cocaine after being returned to the home cage. Control groups were injected with saline at both time points. In separate experiments, rats were pretreated with cocaine or saline and restricted to the home cage. On PD 20, all rats were injected with cocaine (20 mg/kg) and placed in activity chambers where locomotor activity was assessed for 60 min. For comparison purposes, sensitization was also assessed in adult rats. Adult male and female rats exhibited only context-dependent sensitization, whereas preweanling rats showed context-independent sensitization in a variety of conditions (e.g., when pretreated with cocaine in various novel chambers or the home cage). These results suggest that nonassociative mechanisms underlying behavioral sensitization are functionally mature in preweanling rats, but associative processes modulating the strength of the sensitized response do not function in an adult-like manner during the preweanling period.