Role of NMDA and AMPA glutamatergic receptors in the effects of social defeat on the rewarding properties of MDMA in mice
María Pilar García-pardo, José Miñarro, Marta Llansola, Vicente Felipo, M.A. Aguilar
European Journal of Neuroscience October 2, 2018 DOI: 10.1111/ejn.14190 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled animal experiment Peer reviewed |
|---|---|
| Population | Young adult male mice, including mice exposed to social defeat by an aggressive conspecific and undefeated controls |
| Interventions | MDMA Memantine CNQX |
| Dose | MDMA 1.25 mg/kg; memantine 5 or 10 mg/kg; CNQX 0.25, 1 or 5 mg/kg |
| Duration | Four MDMA conditioning sessions on alternating days |
| Measures | conditioned place preference, membrane expression of NMDA and AMPA receptors |
| Topics | MDMA |
| Citations | 26 |
| Key findings | Social defeat prevented MDMA-induced conditioned place preference in mice, and the NMDA antagonist memantine reversed this effect while the AMPA antagonist CNQX did not. Social defeat also decreased membrane expression of several NMDA and AMPA receptor subunits, mainly GluN1 and GluA1. The authors conclude that glutamatergic plasticity is involved in the effects of social defeat stress on MDMA reward. |
Abstract
Exposure to social stress alters the response to drugs of abuse of experimental animals. Changes in the glutamatergic system seem to play a role in the effects of social defeat stress on the rewarding properties of cocaine and amphetamine. The aim of the present study was to evaluate the involvement of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors in the effects of social defeat on the conditioned place preference induced by 3,4-methylenedioxymethamphetamine (MDMA). Our hypothesis was that changes in these receptors could mediate the effects of social defeat on MDMA reward. Young adult male mice were exposed to an episode of social defeat with an aggressive conspecific immediately before each conditioning session with MDMA (1.25 mg/kg, four sessions on alternating days). According to the treatment received before defeats, six groups were used: saline, 5 or 10 mg/kg of memantine (NMDA antagonist) and 0.25, 1 or 5 mg/kg of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (AMPA antagonist). One control group was exposed to exploration before place conditioning. In two additional defeated and control groups, the membrane expression of NMDA and AMPA receptors was determined in the striatum and the hippocampus. Control and memantine-treated groups developed place preference, but not defeated mice treated with saline or CNQX, suggesting that the blockade of NMDA receptors reversed the effects of social defeat. Social defeat decreased the expression of several subunits of NMDA and AMPA receptors, mainly GluN1 and GluA1. These results demonstrated that glutamatergic plasticity is involved in the effects of social defeat stress on MDMA reward.