Individual differences in amphetamine self-administration: the role of the central nucleus of the amygdala

Abstract

Rats categorized as high responder (HR), based on their activity in an inescapable novel environment, self-administer more amphetamine than low responder (LR) rats. The current study examined if the central nucleus of the amygdala (ACe) contributes to the elevated response for amphetamine in HR rats. Male Sprague-Dawley rats were classified as HR and LR rats based on their activity in inescapable novelty and novelty place preference, and then were trained to self-administer amphetamine (0.1 mg/kg/infusion). Once stable responding was achieved, rats received microinfusions of the GABA(A) agonist muscimol (0.5 microg/0.5 microl) or phosphate-buffered saline into the ACe immediately before self-administration of amphetamine (0.1, 0.03, 0.01, or 0.001 mg/kg/infusion) or saline. An additional group of rats was trained to lever press for sucrose rather than amphetamine. Based on the inescapable novelty test, HR rats self-administered more amphetamine than LR rats at the 0.03 and 0.01 mg/kg/infusion unit doses; there were no significant individual differences in amphetamine self-administration based on the novelty place preference test. Inactivation of the ACe with muscimol decreased self-administration at the 0.03 and 0.01 mg/kg/infusion unit doses in HR rats, but had no effect on LR rats. ACe inactivation had no reliable effect on inactive lever responding and appeared to be region specific based on anatomical controls. In addition, while inactivation of the ACe decreased responding for sucrose, inactivation did not differentially affect HR and LR rats. These results suggest that the ACe contributes to the elevated rate of amphetamine self-administration in HR rats.

Figure 1

Microinfusion cannulae placements as verified by thionin-stained sections. Symbols (● amphetamine self-administration;◆ sucrose-maintained responding) represent the most ventral point of the injector tract for each rat on coronal sections based on the atlas of Paxinos and Watson (1998). Numbers indicate the distance from Bregma in millimeters.

Figure 2

Acquisition of amphetamine self-administration (0.1 mg/kg/infusion) in rats classified on inescapable novelty test as HR or LR (A) and in rats classified on novelty place preference test as high novelty seekers or low novelty seekers (B). Data are expressed as mean ± SEM number of amphetamine infusions for the sessions at each FR value. * indicates a significant difference from LR rats (p<0.01).

Figure 3

Effect of muscimol or PBS infusions on the number of amphetamine infusions earned in rats classified on inescapable novelty test as HR (A) or LR (B). Data are expressed as mean ± SEM number of amphetamine infusions for each unit dose. * indicates a significant difference from the PBS group (p<0.01).

Figure 4

Effect of muscimol or PBS infusions on the number of amphetamine infusions earned in rats classified on novelty place preference test as high novelty seekers (A) or low novelty seekers (B). Data are expressed as mean ± SEM number of amphetamine infusions for each unit dose. * indicates a significant difference from the PBS group (p<0.01).

Figure 5

Mean ± SEM number of amphetamine infusions (0.1 mg/kg/infusion) earned following the initial set of microinfusions (Test 1) and final set of microinfusions at the end of the experiment (Test 2).

Figure 6

Time course effect of muscimol or PBS infusions on responding for amphetamine in rats classified on inescapable novelty test as HR or LR. Data are expressed as mean ± SEM number of amphetamine infusions across 5-min blocks for the 0.1 (A and B) and 0.03 (C and D) mg/kg/infusion unit doses in HR rats (A, C) or LR rats (B, D). * indicates a significant difference from the PBS group (p<0.01).