Abstract
Rationale
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.
Objective
To investigate the involvement of insular muscarinic acetylcholine receptors (mAChRs) in the processing of drug memory.
Method
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.
Results
Insular microinjections of the nonselective mAChR antagonist, scopolamine, and the M1 antagonist, pirenzepine, significantly inhibited CPP expression in both contextual cue- and priming-induced CPP reinstatement; the M1 agonist, MCN-A-343, and the M4 antagonist, tropicamide, enhanced CPP expression. The M4 agonist, LY2033298, inhibited CPP expression. The M2 antagonist, methoctramine, and M3 antagonist, 4-DAMP, had no effect on CPP expression.
Conclusion
Our results demonstrate that insular mAChRs play a role in the processing of drug memory. M1 and M4 mAChRs work paradoxically; M1 activation and M4 inhibition attenuate the expression of drug memory, while M1 inhibition and M4 activation augment the expression of drug memory.
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Acknowledgments
This project was jointly sponsored by the National Science Foundation (no. 30873051, 81271473) and Beijing Municipal Natural Science Foundation (no. 7112087) of China.
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Wu, W., Li, H., Liu, Y. et al. Involvement of insular muscarinic cholinergic receptors in morphine-induced conditioned place preference in rats. Psychopharmacology 231, 4109–4118 (2014). https://doi.org/10.1007/s00213-014-3550-1
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DOI: https://doi.org/10.1007/s00213-014-3550-1