Memantine blocks sensitization to the rewarding effects of morphine

Knowledge regarding the specific brain changes and neural plasticity processes produced by repeated drug exposure may be used to advance the understanding of the neurobiology of addiction in order to design appropriate medications. In the present study, the influence of N-methyl-d-aspartate (NMDA) glutamatergic receptors on sensitization to the motor and rewarding effects of morphine was evaluated. The effects of pre-exposure to saline or 20 mg/kg morphine plus the NMDA receptor antagonist memantine (10 or 20 mg/kg) on motor activity and place conditioning induced by a low dose of morphine (2 mg/kg) were assessed. The dose of 2 mg/kg of morphine was ineffective in mice pre-exposed to saline but induced a clear conditioned place preference (CPP) in those pre-exposed to morphine. Conversely, animals pre-exposed to morphine plus memantine did not acquire CPP. Only those pre-exposed to morphine presented an increased motor response to morphine 2 mg/kg. Our results demonstrate that NMDA glutamatergic receptors are implicated in the development of sensitization to the conditioned rewarding effects of morphine.