Glutamate and Addiction

National Institute On Drug Abuse

Investigators

Linked publications & trials

Abstract

In one of our recent reports, we used wild-type (WT) and mGluR2 mutant rats, in which no mGluR2 is expressed, to study whether mGluR2 loss alters cocaine-taking and cocaine-seeking behaviors in different stages of the drug addiction cycle. We found that the mGluR2 gene mutation abolished mGluR2 expression and significantly altered cocaine-taking and cocaine-seeking behaviors. mGluR2 mutant rats showed significant increases in basal extracellular levels of glutamate and DA in the NAc, and reduced sensitivity to cocaine reward, as assessed by requiring more cocaine to reach satiation when the drug was freely available and the cessation of drug-seeking behavior sooner than controls when the response requirement was increased. mGluR2 mutant rats also show a lower propensity to relapse after a period of cocaine abstinence, an effect associated with reduced cocaine-induced DA and glutamate overflow in the NAc. These findings suggest that mGluR2 polymorphisms or reduced availability of mGluR2 might be risk factors for the initial development of cocaine use but could actually protect against addiction by reducing sensitivity to cocaine reward. Future studies will be focused on specific glutamate pathways for their role in mediating drug reward, exercise reward, and specifically in mediating cannabis reward and aversion.