The contribution of the central nucleus of the amygdala to individual differences in amphetamine-induced hyperactivity

Abstract

Rats classified as high responders (HR) based on their response to an inescapable novel environment self-administer more amphetamine and have greater amphetamine-induced sensitization than rats classified as low responders (LR). Recent research suggests that the central nucleus of the amygdala (ACe) contributes to the elevated self-administration in HR rats. Therefore, the current study examined the role of the ACe in the expression of both amphetamine-induced sensitization and conditioned hyperactivity in HR and LR rats. Male Sprague-Dawley rats were screened for their response to inescapable novelty and classified as HR or LR rats. Rats were implanted with bilateral cannulae into the ACe and received amphetamine (1.0 mg/kg, s.c.) or saline injections immediately prior to 1-h locomotor sessions. Following five training sessions, all rats received an infusion of muscimol (0.5 microg/0.5 microl) or phosphate buffered saline (PBS) followed by a saline injection to measure conditioned hyperactivity. HR rats displayed conditioned hyperactivity, while LR rats did not, suggesting that HR and LR rats differ in the expression of conditioned hyperactivity. While ACe inactivation attenuated the expression of conditioned hyperactivity, it did not differentially affect HR and LR rats. Following additional training and a 10-day rest period, all rats were then tested for amphetamine-induced sensitization (1.0 mg/kg) following an infusion of muscimol or PBS. Inactivation of the ACe attenuated the expression of sensitization only in HR rats. These results suggest the ACe contributes to the greater amphetamine sensitization in HR rats.

Figure 1

Shaded regions indicate the location of cannulae placements as verified by thionin-stained sections for HR () and LR () rats. The shaded regions represent the most ventral point of the injector tracts on coronal sections based on the atlas of Paxinos and Watson (1998). Numbers indicate the distance from Bregma in millimeters.

Figure 2

Figure 2A & B: The mean (± S.E.M.) total distance traveled (cm) for rats in the Paired, Unpaired and Control groups during sessions 1–5 of acquisition training. (A): HR and LR groups. (B) HNS and LNS groups. Asterisks (*) indicate a significant difference (p<.001) in Paired groups relative to Unpaired and Control groups. Numerical signs (#) indicate a significant difference (p<.05) between HR and LR rats.

Figure 3

The mean (± S.E.M.) total distance traveled (cm) for rats in the Paired, Unpaired and Control groups during the conditioned-hyperactivity test. Asterisks (*) indicate a significant difference (p<.01) in Paired groups relative to Unpaired and Control groups. Numerical signs (#) indicate a significant difference (p<.01) between Muscimol treatment groups relative to PBS treatment groups.

Figure 4

Figure 4A & B: The mean (± S.E.M.) total distance traveled (cm) for HR and LR rats in the Paired, Unpaired and Control groups during the conditioned-hyperactivity test. (A): HR rats treated with PBS and muscimol. (B). LR rats treated with PBS and muscimol. Asterisks (*) indicate a significant difference (p<.01) from the Paired groups. Numerical signs (#) indicate a significant difference (p<.001) between PBS and muscimol treatment groups.

Figure 5

The mean (± S.E.M.) total distance traveled (cm) for HR and LR rats in the Paired, Unpaired and Control groups during sessions 1–5 of sensitization training. Asterisks (*) indicate a significant difference (p<.001) in Paired groups relative to Unpaired and Control groups. Numerical sign (#) indicates a significant difference (p<.05) between HR and LR rats.

Figure 6

The mean (± S.E.M.) total distance traveled (cm) for rats in the Paired, Unpaired and Control groups during the sensitization test. Asterisks (*) indicate a significant difference (p<.01) in Paired groups relative to Unpaired and Control groups.

Figure 7

Figure 7A & B: The mean (± S.E.M.) total distance traveled (cm) for HR and LR rats in the Paired, Unpaired and Control groups during the sensitization test. (A): HR rats treated with PBS and muscimol. (B). LR rats treated with PBS and muscimol. Asterisks (*) indicate a significant difference (p<.01) from Control groups. Numerical signs (#) indicate a significant difference (p<.05) between PBS and muscimol treatment groups.