Additive Effects of Coadministration of A2A Receptor Agonist CGS-21680and mGluR5 Antagonist MPEP on the Development and Expression of Methamphetamine-Induced Locomotor Sensitization in Rats

Abstract

Background. Accumulating evidence suggests that A2A adenosine receptors and metabotropic glutamate receptors 5 (mGluR5) may modulate the nucleus accumbens (nAcc) dopamine neurotransmission. This study examined the effects of coadministration of the A2A receptor agonist CGS-21680 and the mGluR5 antagonist MPEP on the development and expression of methamphetamine (METH)-induced locomotor sensitization. Methods. Rats were treated with different doses of CGS (0.1 mg/kg, 0.2 mg/kg or 0.4 mg/kg) or MPEP (1.0 mg/kg, 3.0 mg/kg or 10.0 mg/kg) or coadministration of CGS (0.1 mg/kg, 0.2 mg/kg or 0.4 mg/kg) with MPEP (3.0 mg/kg) plus METH (1.0 mg/kg). For the challenge test, rats received a single injection of METH (1.0mg/kg). In experiments to assess the expression of METH-induced locomotor sensitization, rats were treated with a daily dose of METH (1.0mg/kg), and the challenge test was preceded by injection of CGS (0.1 mg/kg, 0.2 mg/kg or 0.4 mg/kg), MPEP (1.0 mg/kg, 3.0 mg/kg or 10.0 mg/kg) or coadministration of CGS (0.1 mg/kg, 0.2 mg/kg or 0.4 mg/kg) with MPEP (3.0 mg/kg) plus METH (1.0 mg/kg). Results. The data showed that CGS and MPEP treatment prevented both the development and expression of METH-induced locomotor sensitization. Furthermore, CGS increased the effects of a low MPEP dose on METH-induced locomotor sensitization under both conditions. Conclusion. These findings suggest the potential utility of adenosine A2A receptors and mGluR5 ligands to treat psychostimulant addiction.