Involvement of insular muscarinic cholinergic receptors in morphine-induced conditioned place preference in rats

Drug addiction represents a pathological usurpation of neural processes involved in learning and memory. Retrieval of drug-related memories can result in drug craving and relapse. Recently, the insula was identified as part of the neuronal circuit responsible for the processing of drug memory; however, its precise role remains unclear. To investigate the involvement of insular muscarinic acetylcholine receptors (mAChRs) in the processing of drug memory. The morphine-induced conditioned place preference (CPP) was used to assess drug memory. All rats were first trained with morphine to establish the CPP. Sub-groups of these rats were used for contextual cue-induced CPP reinstatement. Other sub-groups of rats underwent extinction of the CPP, and 5 m/kg morphine was used for priming-induced CPP reinstatement. Microinjection of mAChR antagonists or agonists into the insula was performed prior to the CPP tests in order to evaluate their effect on CPP expression. Insular microinjections of the nonselective mAChR antagonist, scopolamine, and the M-1 antagonist, pirenzepine, significantly inhibited CPP expression in both contextual cue- and priming-induced CPP reinstatement; the M-1 agonist, MCN-A-343, and the M-4 antagonist, tropicamide, enhanced CPP expression. The M-4 agonist, LY2033298, inhibited CPP expression. The M-2 antagonist, methoctramine, and M-3 antagonist, 4-DAMP, had no effect on CPP expression. Our results demonstrate that insular mAChRs play a role in the processing of drug memory. M-1 and M-4 mAChRs work paradoxically; M-1 activation and M-4 inhibition attenuate the expression of drug memory, while M-1 inhibition and M-4 activation augment the expression of drug memory.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000343721600003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701NeurosciencesPharmacology & PharmacyPsychiatrySCI(E)8ARTICLEzhaihf@hsc.pku.edu.cn214109-411823