Role of NMDA and AMPA glutamatergic receptors in the effects of social defeat on the rewarding properties of MDMA in mice

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...

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Published in:The European journal of neuroscience 2019-08, Vol.50 (3), p.2623-2634
Main Authors: García‐Pardo, M. P., Miñarro, J., Llansola, M., Felipo, V., Aguilar, M. A.
Format: Article
Language:English
Subjects:
Amphetamines
Cocaine
conditioned place preference
Drug abuse
drug addiction
Ecstasy
glutamate receptor
Glutamatergic transmission
Glutamic acid receptors (ionotropic)
MDMA
Memantine
N-Methyl-D-aspartic acid receptors
Neostriatum
Place preference conditioning
Receptor mechanisms
Reinforcement
Social interactions
stress
α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
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Summary: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. Acquisition of conditioned place preference induced by 3,4‐methylenedioxymethamphetamine (MDMA) (1.25 mg/kg) in young adult male mice is impaired by exposure to social defeat before each conditioning session with the drug. Administration of the N‐methyl‐D‐aspartate (NMDA) antagonist memantine reversed the impairing effects of social defeat on MDMA conditioned place preference. Exposure to social defeat decreased the expression of several subunits of NMDA and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors, mainly GluN1 and GluA, in the striatum and hippocampus, 48 h after the last episode of social defeat.
ISSN:0953-816X
1460-9568
DOI:10.1111/ejn.14190