The metabotropic glutamate 5 receptor is necessary for extinction of cocaine-associated cues

British Journal of Pharmacology
Christina PerryAndrew J Lawrence

Abstract

There is currently no medication approved specifically to treat cocaine addiction. Behavioural interventions such as cue exposure therapy (CET) rely heavily on new learning. Antagonism of the metabotropic glutamate 5 (mGlu5 ) receptor has emerged as a potential treatment, by reducing the reinforcing properties of cocaine. However, mGlu5 receptor activity is necessary for learning; therefore, such agents could interfere with behavioural treatments. We used a novel rodent model of CET to test the effects of mGlu5 negative and positive allosteric modulators (NAM and PAM) on behavioural therapy. Rats were trained to press a lever for cocaine in the presence of a discrete cue [conditioned stimulus (CS)] and then extinguished in the absence of the CS. Following lever extinction, half the rats received CS extinction in the same chambers but with the levers withdrawn; the remaining rats received no CS extinction. Before this session, rats received a systemic administration of either vehicle or a mGlu5 NAM (MTEP, experiment 1) or PAM (CDPPB, experiment 2). Cue-induced reinstatement was tested in a drug-free session the following day. At reinstatement, rats that had received CS extinction showed reduced responding. This effect was attenu...Continue Reading

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Citations

Jun 18, 2016·Frontiers in Physiology·Paula F KinoshitaCristoforo Scavone
Sep 11, 2016·Neurobiology of Learning and Memory·Heather B MadsenJee Hyun Kim
Oct 28, 2016·Genes, Brain, and Behavior·C J Perry, A J Lawrence
Oct 17, 2016·The International Journal of Neuropsychopharmacology·Hanne Mette HoffmannMichel Vignes
Aug 26, 2019·Psychopharmacology·Christina Gobin, Marek Schwendt
Feb 14, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Shaun Yon-Seng KhooNadia Chaudhri
Mar 17, 2020·Cellular and Molecular Life Sciences : CMLS·Brooke N Bender, Mary M Torregrossa
Dec 29, 2020·Pharmacology & Therapeutics·Ewa Niedzielska-AndresEdmund Przegaliński

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