Effects of CNQX and MPEP on sensitization to the rewarding effects of morphine

The present study was conducted to evaluate the influence of the glutamatergic receptors α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and metabotropic glutamate 5 (mGlu5) receptors on sensitization to the rewarding effects of morphine. The effects of pre-treatment with saline or 20 mg/kg morphine plus the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (5 or 10 mg/kg) or the metabotropic Glu5 receptor antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) (5 or 10 mg/kg) on the place conditioning induced by a low dose of morphine (2 mg/kg) were assessed. The 2 mg/kg dose of morphine was ineffective in animals pre-treated with saline but induced a clear conditioned place preference (CPP) in mice pre-treated with morphine alone and morphine plus any of the MPEP doses or the lowest dose of CNQX. Conversely, animals pre-treated with morphine plus 10 mg/kg of CNQX did not acquire CPP. Our results suggest that AMPA glutamate receptors are involved in the development of sensitization to the conditioned rewarding effects of morphine.