Blockade of group II, but not group I, mGluRs in the rat nucleus accumbens inhibits the expression of conditioned hyperactivity in an amphetamine-associated environment

Abstract

Environmental stimuli associated with amphetamine (AMPH) can elicit conditioned locomotion in rats, and the nucleus accumbens (NAcc) is known to be important in this process. This study examined the contribution of metabotropic glutamate receptors (mGluRs) in the NAcc to the expression of conditioned locomotion in an AMPH-associated environment. Rats in different groups were administered injections in five 3-day blocks: Paired, AMPH (1.0 mg/kg, IP) in locomotor activity boxes on day 1 and saline in their home cages on day 2; Unpaired, saline in the activity boxes on day 1 and AMPH in their home cages on day 2; or Control, saline in both environments. No injections were administered on day 3 of each block. One week after the last conditioning block, all rats were tested for their conditioned locomotor response in the activity boxes for 1 h following an IP saline injection. In Paired rats, this injection was preceded by a bilateral microinjection into the NAcc of saline, the group I mGluR antagonist, AIDA (0.5, 5.0 nmol/side), or the group II mGluR antagonist, EGLU (0.5, 5.0 nmol/side). Unpaired and Control rats received NAcc saline. As expected, Paired rats showed both increased locomotor activity and rearing compared to rats in either the Unpaired or Control groups. However, the expression of this conditioned hyper-locomotion was dose-dependently inhibited by NAcc EGLU, but not by AIDA. These results suggest that activation of group II, but not of group I, mGluRs in the NAcc contributes to the expression of conditioned locomotion in an environment associated with amphetamine.