The mGlu2/3 receptor agonist LY379268 blocks the expression of locomotor sensitization by amphetamine.

The present experiments assessed the effect of the Group II-specific metabotropic glutamate receptor (mGluR) agonist, LY379268, on the expression of the locomotor sensitization observed following repeated exposure to amphetamine (AMPH). Rats in different groups were administered five injections of AMPH (1 mg/kg ip), one injection every 2-3 days. Two weeks after the last injection, rats were challenged with either AMPH (1 mg/kg ip) or AMPH coinjected with LY379268 (1 mg/kg ip). As expected, AMPH produced levels of locomotion that increased progressively from the first to the fifth injection. This locomotor sensitization was still evident 2 weeks later in rats challenged with AMPH. Rats challenged on this test with AMPH+LY379268, however, showed levels of locomotion similar to those observed following the first AMPH injection. These results indicate that Group II mGluRs can play an important role in the expression of locomotor sensitization by AMPH. The ability of Group II mGluR activation to block the expression of sensitization indicates that it can be targeted as a possible molecular candidate for the development of therapeutic drugs directed at drugs of abuse.