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

Abstract

Rationale: Preweanling rats, unlike adults, exhibit context-independent behavioral sensitization after a single pretreatment injection of cocaine.

Objective: The purpose of this study was to examine environmental factors modulating one- and three-trial sensitization in preweanling rats.

Methods: 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.

Results: 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).

Conclusions: 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.

Fig. 1

Mean distance traveled scores (±SEM) of preweanling rats injected with 30 mg/kg cocaine (filled squares) or saline (open circles) and placed in activity chambers on the three pretreatment days (i.e., PD 17–PD 19). *Significantly different from rats injected with saline on the same time block (P<0.05).

Fig. 2

Mean distance traveled scores (±SEM) of preweanling rats (n = 8 per group) given a challenge injection of cocaine (20 mg/kg, IP) prior to placement in activity chambers on PD 20. Rats in the Cocaine-Chamber groups (filled squares) had been injected with cocaine (20 mg/kg, IP) before being placed in their respective chambers (activity, large, or small chambers) on PD 17–PD 19, while rats in the Saline-Chamber groups (filled triangles) had been injected with cocaine 30 min after being returned to the home cage. The Control groups (open circles) were injected with saline at both time points. The inset shows mean distance traveled collapsed across time blocks 1–12. *Significantly different from the control group (P<0.05).

Fig. 3

Mean distance traveled scores (±SEM) of preweanling rats (n = 8 per group) given a challenge injection of cocaine (20 mg/kg, IP) prior to placement in the activity chambers on PD 20. On PD 17–PD 19, rats had been restricted to their home cage and injected with either 30 mg/kg cocaine (filled squares) or saline (open circles). The inset shows mean distance traveled collapsed across time blocks 1–12. *Significantly different from the Saline-Home group (P<0.05).

Fig. 4

Mean distance traveled scores (±SEM) of preweanling rats (n = 8 per group) given a challenge injection of cocaine (20 mg/kg, IP) prior to placement in activity chambers on PD 20. Rats in the Cocaine-Chamber groups (filled squares) had been injected with cocaine (20 mg/kg, IP) before being placed in their respective chambers (activity, large, or small chambers) on PD 19, while rats in the Saline-Chamber groups (filled triangles) had been injected with cocaine 30 min after being returned to the home cage. The Control groups (open circles) were injected with saline at both time points. The inset shows mean distance traveled collapsed across time blocks 1–12. *Significantly different from the control group (P<0.05).

Fig. 5

Mean distance traveled scores (±SEM) of preweanling rats (n = 8 per group) given a challenge injection of cocaine (20 mg/kg, IP) prior to placement in the activity chambers on PD 20. On PD 19, rats had been restricted to their home cage and injected with either 30 mg/kg cocaine (filled squares) or saline (open circles). The inset shows mean distance traveled collapsed across time blocks 1–12. *Significantly different from the Saline-Home group (P<0.05).

Fig. 6

Mean distance traveled scores (±SEM) of adult rats injected with 30 mg/kg cocaine or saline and placed in activity chambers on the pretreatment day (PD 79). Cocaine-Female = filled squares; Cocaine-Male = filled circles; Saline-Female = open squares; Saline-Male = open circles. *Significantly different from rats injected with saline on the same time block (P<0.05).

Fig. 7

Mean distance traveled scores (±SEM) of adult male and female rats (n = 8 per group) given a challenge injection of cocaine (20 mg/kg, IP) prior to placement in the activity chambers on PD 80. On PD 79, rats had been transported to either the activity chambers (upper graph) or restricted to the home cage (lower graph), with drug pretreatments being the same as described in Figs. 4 and 5. The inset shows mean distance traveled collapsed across both sex and time blocks 1–12. *Significantly different from the Activity-Control group (P<0.05).

Fig. 8

Mean distance traveled scores (±SEM) of adult male and female rats (n = 8–10 per group) given a challenge injection of cocaine (20 mg/kg, IP) prior to placement in the activity chambers on PD 80. On PD 79, rats had been restricted to their home cage and injected with either 30 mg/kg cocaine (filled squares) or saline (open circles). The inset shows mean distance traveled collapsed across time blocks 1–12.