The role of amygdala group I mGluRs in synaptic plasticity and conditioned place preference in rodents



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Currently, there are no approved medications for treating cocaine addiction, and cocaine addicts are highly prone to relapse. Cocaine cravings or seeking is difficult to control because of contextual cues and adequate treatment is not available. Previous studies found that group I metabotropic glutamate receptor (mGluR) antagonists can block the induction of conditioned place preference (CPP), a measure of cocaine seeking behavior, but their functions after clinically relevant withdrawal periods are not known. Our study showed that group I mGluR antagonists failed to block the expression of cocaine-induced CPP. Furthermore, the amygdala is known to be involved in the learned associations between cocaine and the cocaine-taking environment; changes in these associations are reflected in an in vitro model of plasticity, long-term potentiation, in amygdala pathways. Chronic cocaine withdrawal did not affect mGluR5-mediated LTP in the basolateral to central amygdala pathway. However, mGluR1-mediated LTP was reduced after cocaine administration and withdrawal and was partially due to GABA inhibition via endocannabinoids.