Blockade of group II metabotropic glutamate receptors in the nucleus accumbens produces hyperlocomotion in rats previously exposed to amphetamine

The neurotransmitter glutamate is known to participate in both the induction and expression of locomotor sensitization by psychostimulant drugs like amphetamine. Previously, it was reported that subtype nonselective blockade of metabotropic glutamate receptors (mGluRs) in the nucleus accumbens (NAcc) produces hyperlocomotion in rats previously exposed to amphetamine. The present experiments examined whether group II mGluRs may contribute to this effect. Rats in different groups were administered five injections of either saline or amphetamine (1.0 mg/kg, i.p.), one injection given every third day. Two weeks later, they were tested for 2 h following an injection of either saline or the group II mGluR antagonist LY341495. In one experiment, test injections were administered systemically (saline or LY341495, 1.0 mg/kg, i.p.). Rats previously exposed to amphetamine showed a greater locomotor response to LY341495 on the test compared to controls previously exposed to saline. This hyperlocomotor response was absent in rats tested with a combination of LY341495 and the group II mGluR agonist LY379268 (1.0 mg/kg, i.p.). In a second experiment, different rats were tested following microinjections into the NAcc (saline or LY341495, 0.1, 10 or 100 μg/0.5 μl/side). Again, rats previously exposed to amphetamine showed a greater dose-dependent locomotor response to LY341495 on the test relative to saline-exposed controls. Locomotor activity in saline-exposed rats challenged with LY341495 did not differ from that observed in rats previously exposed and tested with saline in either experiment. These results indicate that group II mGluRs, particularly those found in the NAcc, are well positioned to modulate the expression of locomotor sensitization by amphetamine.