Injection of CART (cocaine- and amphetamine-regulated transcript) peptide into the nucleus accumbens reduces cocaine self-administration in rats

Abstract

Cocaine- and amphetamine-regulated transcript (CART) peptides appear to modulate various effects of psychostimulant drugs. Injections of CART peptide into the nucleus accumbens (NAcc) inhibit locomotion produced by systemic injections of the psychostimulants cocaine and amphetamine. Intra-NAcc injections of CART peptide also inhibit locomotion produced by microinfusions of dopamine into the NAcc, suggesting that the effects of CART peptides may be due to an interaction with the dopaminergic system in the NAcc. We sought to determine if this inhibitory effect of CART peptide generalizes to other measures of dopaminergic function such as reward/reinforcement by testing the effect of bilateral intra-NAcc CART infusions (0, 0.25, 1.0 and 2.5 microg per side) on cocaine and food self-administration. One group of rats self-administered cocaine (0.75 mg/kg per 140 microl IV infusion) on a progressive ratio schedule. A separate group received 45 mg food pellets on the same progressive ratio schedule. Bilateral intra-NAcc injections of CART peptide dose-dependently decreased the number of cocaine infusions, the breakpoint of cocaine self-administration, and the total number of bar presses on the cocaine-associated lever. There were no effects of CART injections on the breakpoint for food reward. Thus, we conclude that injections of CART into the NAcc appear to functionally antagonize a major site of action for cocaine self-administration in rats.

Figure 1

Locations of the intra-NAcc injection sites are depicted on schematic drawings of coronal slices. Numbers represent mm from Bregma according to the atlas of Paxinos & Watson (1998). Injection sites in rats that completed the cocaine self-administration study are depicted by red circles. Injection sites in rats used in the food self-administration study are shown in blue triangles.

Figure 2

A. The effect of intra-NAcc infusions of CART peptide on the number of cocaine infusions taken relative to baseline (grey bars; average of the 2 days prior to testing), CART microinjection day (black bars) and recovery (average of the 2 days after treatment; white bars). Data are MEAN±SEM. The n/group was 8,7,8, and 11 for the aCSF, 0.25, 1.0 and 2.5 µg CART injection groups, respectively. The asterisk denotes a significant difference from the treatment day value obtained for aCSF (p<0.05). B. The effect of the CART peptide infusions on the absolute number of inactive lever presses on baseline (grey bars), CART microinjection day (black bars) and recovery (white bars). There were no significant differences between the treatment groups. These data are not depicted as a percent of baseline because in some animals, the number of inactive lever presses was 0. Data are MEAN±SEM. The n/group was 8,7,8, and 11 for aCSF, 0.25, 1.0 and 2.5 µg CART peptide injection groups, respectively.

Figure 3

The effect of intra-NAc injection of CART peptide (and aCSF) on food pellets received on a progressive ratio reinforcement schedule. Data are MEAN±SEM. N=6 per group.