Centre for Youth Mental Health - Research Publications
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ItemMGLU5 receptors are necessary for extinction of drug associated cues and contexts(Wiley, 2017-08-01)Drug-associated cues and contexts are strong predictors of relapse. We used complex behavioural preparations to examine whether extinction of such cues reduces their capacity to trigger drug-seeking. We also examined whether the mGlu5 receptor is necessary for extinction learning. In Experiment 1, rats were trained to lever press for cocaine. Once stable responding was established, the context was extinguished by replacing the rats in the chambers, but with no opportunity to respond (levers were retracted). Control group remained in their home cage. An mGlu5 receptor negative allosteric modulator (MTEP) or vehicle was administered immediately after context extinction sessions. During subsequent drug-induced reinstatement, rats responded less if they had received context extinction; however, this effect was attenuated where MTEP had been applied. In Experiment 2, rats were trained to lever press for cocaine, now paired with a cue light. To extinguish the cue, half of the rats were placed in the chambers and given non-reinforced presentations of the cue, but with the levers retracted. Control rats remained in home cage. All rats received either MTEP or vehicle 20 minutes prior. Cue-induced reinstatement was tested the following day by re-pairing the lever with the light. Rats gave fewer drug-seeking responses following cue extinction. This effect was attenuated by MTEP. Experiment 3 followed the same protocol as Experiment 2, except that a positive allosteric modulator CDPPB or vehicle was administered 20 minutes before CS extinction. At reinstatement, cue-elicited cocaine seeking was lower for the animals that had previously been administered CDPPB, regardless of extinction condition. This study highlights the important role cues and contexts play in driving drug-seeking behaviour during reinstatement. It also shows that mGlu 5 signalling is necessary for extinction of drug-cue associations, and that mGlu5 positive allosteric modulators are promising targets for treating cocaine addiction.