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The mGlu5 receptor regulates extinction of cocaine-driven behaviours

2014; Elsevier BV; Volume: 137; Linguagem: Inglês

10.1016/j.drugalcdep.2014.01.017

1879-0046

M. K. Bird, Peter Lohmann, Billy West, Robyn M. Brown, Jeppe Kirchhoff, Clarke R. Raymond, Andrew J. Lawrence,

Neurotransmitter Receptor Influence on Behavior

There is extensive evidence implicating the metabotropic glutamate 5 (mGlu5) receptor in aspects of addiction-related behaviours. Here, we used a well-characterized line of mGlu5-deficient mice to further examine the role of this receptor in cocaine-driven behaviours. We confirmed the previously reported deficit in hippocampal long-term potentiation and associated spatial learning impairment. Despite a spatial learning deficit, mGlu5-deficient mice developed and maintained a conditioned place preference to cocaine, suggesting cocaine reward and Pavlovian conditioning are intact in these animals. Notably, however, mGlu5-deficient mice exhibited a marked deficit in the extinction of a cocaine-conditioned place preference compared to wild type littermates. Moreover, in a fixed ratio operant intravenous self-administration paradigm, both genotypes showed similar responding for cocaine over two different doses, while mGlu5-deficient mice displayed enhanced responding on a progressive ratio schedule. In addition, cue-induced drug-seeking after abstinence was exaggerated in mGlu5-deficient mice. Collectively, these findings suggest that while the mGlu5 receptor may be involved in mediating the rewarding effects of cocaine, it appears necessary for the extinction of cocaine-driven behaviours.