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


METHODS
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.


CONCLUSIONS
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.
School of Medicine, Ningbo University, 315010, Ningbo, China.
Wei
W
Wu
Hui
H
Li
Yu
Y
Liu
Xinjie
X
Huang
Lei
L
Chen
Haifeng
H
Zhai
D000818:Animals; D001245:Association Learning / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D009294:Narcotics; D009020:Morphine