Importance of associative learning processes for one-trial behavioral sensitization of preweanling rats

Abstract

During adulthood, associative learning is necessary for the expression of one-trial behavioral sensitization; however, it is uncertain whether the same associative processes are operative during the preweanling period. Two strategies were used to assess the importance of associative learning for one-trial behavioral sensitization of preweanling rats. In the initial experiments, we varied both the sequence and time interval between presentation of the conditioned stimulus (CS, novel environment) and unconditioned stimulus (US, cocaine). In the final experiment, we determined whether electroconvulsive shock-induced retrograde amnesia would disrupt one-trial behavioral sensitization. Results showed that robust-sensitized responding was apparent regardless of the sequence in which cocaine and the novel environment (the presumptive CS) were presented. Varying the time between CS and US presentation (0, 3, or 6 h) was also without effect. Results from experiment 3 showed that single or multiple electroconvulsive shock treatments did not alter the expression of the sensitized response. Therefore, these data indicated that one-trial behavioral sensitization of preweanling rats was exclusively mediated by nonassociative mechanisms and that associative processes did not modulate sensitized responding. These findings are in contrast to what is observed during adulthood, as adult rats exhibit one-trial behavioral sensitization only when associative processes are operative.

Fig 1

Mean distance traveled (+SEM) on the pretreatment day (i.e., PD 19) of Experiment 1. Rats (n = 8 per group) were injected with saline or 30 mg/kg cocaine prior to placement in the activity chambers. *Significantly different from the saline group when collapsed across time blocks 1–6 (Drug main effect, P < 0.001). † Significantly different from the saline group on the same time block (Drug × Time Block interaction and Tukey tests, P < 0.05).

Fig. 2

Mean distance traveled (±SEM) of rats (n = 8 per group) given a challenge injection of cocaine (20 mg/kg, i.p.) on the test day (PD 20) of Experiment 1. On the pretreatment day (PD 19), rats were injected with cocaine while being placed in the activity chambers (i.e., the Simultaneous groups) or 0.5 h (upper graph), 3 h (middle graph), or 6 h (lower graph) after being returned to the home cage (i.e., the Trace groups). The Acute Controls received two injections of saline. *Significantly different from the Acute Control group when collapsed across time blocks 1–12 (Group main effect and Tukey tests, P < 0.05).

Fig 3

Mean distance traveled (+SEM) on the pretreatment day (i.e., PD 19) of Experiment 2. Rats (n = 8 per group) were injected with saline or 30 mg/kg cocaine 0, 3, or 6 h prior to placement in the activity chambers. *Significantly different from the saline group when collapsed across time blocks 1–6 (Drug main effect and Tukey tests, P < 0.05).

Fig. 4

Mean distance traveled (±SEM) of rats (n = 8 per group) given a challenge injection of cocaine (20 mg/kg, i.p.) on the test day (PD 20) of Experiment 2. On the pretreatment day (PD 19), rats were injected with cocaine 3 h (upper graph) or 6 h (lower graph) before being placed in the activity chamber (i.e., the Backward groups) or while being placed in the activity chambers (i.e., the Simultaneous groups). The Acute Controls received two injections of saline. *Significantly different from the Acute Control group when collapsed across time blocks 1–12 (Group main effect and Tukey tests, P < 0.05).

Fig. 5

Mean distance traveled (+SEM) of rats (n = 8 per group) given a challenge injection of cocaine (20 mg/kg, i.p.) on the test day (PD 20) of Experiment 2. On the pretreatment day (PD 19), all rats were restricted to the home cage (i.e., they were never exposed to the activity chamber) and injected with either cocaine (i.e., the Unpaired group) or saline (i.e., the Acute Control group). *Significantly different from the Acute Control group when collapsed across time blocks 1–12 (Group main effect, P < 0.001).

Fig. 6

Mean distance traveled (±SEM) of rats (n = 8 per group) given a challenge injection of cocaine (20 mg/kg, i.p.) on the test day (PD 20) of Experiment 3a. On the pretreatment day (PD 19), rats received their first injection (either saline or 30 mg/kg cocaine) while being placed in the activity chamber and then received their second injection 0.5 h after being returned to the home cage. Rats received a single sham or ECS treatment 1 or 4 h after completion of behavioral testing on PD 19. *Significantly different from the Acute Control group when collapsed across time blocks 1–12 (Group main effect and Tukey tests, P < 0.05).

Fig. 7

Mean distance traveled (±SEM) of rats (n = 8 per group) given a challenge injection of cocaine (20 mg/kg, i.p.) on the test day (PD 21) of Experiment 3b. On the pretreatment day (PD 19), rats received their first injection (either saline or 30 mg/kg cocaine) while being placed in the activity chamber and then received their second injection 0.5 h after being returned to the home cage. Rats received three sham (upper graph) or ECS (lower graph) treatments on PD 19 and PD 20 (i.e., 1, 25, and 29 h after completion of behavioral testing). *Significantly different from the Acute Control group when collapsed across time blocks 1–12 (Group main effect and Tukey tests, P < 0.05).