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The muscarinic agonist pilocarpine modifies cocaine-reinforced and food-reinforced responding in rats

comparison with the cholinesterase inhibitor tacrine

Grasing, Kenneth W.a,c; Xu, Haiyangb; Idowu, Jessica Y.a

doi: 10.1097/FBP.0000000000000472
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Activation of muscarinic receptors in the brain antagonizes the actions of cocaine, blocking both its discriminative stimulus and reinforcing properties. Pilocarpine is a nonselective muscarinic agonist that is used clinically, but has not been well characterized for its actions during cocaine-reinforced behavior. This study evaluated its effects on cocaine-reinforced and food-reinforced behaviors in rats, using the cholinesterase inhibitor tacrine as a comparator. Intraperitoneal pilocarpine or tacrine at doses of 1.0 mg/kg or more attenuated self-administration of low-dose cocaine (0.1 mg/kg injection) but also increased oral movements. Pilocarpine was less potent than tacrine in decreasing responding supported by low or intermediate amounts of liquid food. Combined treatment with pilocarpine and tacrine was more effective than either compound alone in attenuating self-administration of intermediate-dose cocaine. At a low (0.66 mg/kg) dose which did not modify reinforced responding, pilocarpine increased nonspecific behavior (sniffing, rearing, and activity) in cocaine-reinforced but not in food-reinforced animals; with greater doses increasing cholinergic or gastrointestinal signs. These effects were most consistently correlated with changes in reinforcement in rats responding for cocaine relative to food-reinforced animals. Overall, pilocarpine exhibited modest selectivity for attenuating self-administration of low-dose cocaine without affecting a nondrug reinforcer.

aSubstance Abuse Research Laboratory, Kansas City Veterans Affairs Medical Center, Kansas City, Missouri

bDepartment of Biological Science, Florida State University, Tallahassee, Florida

cDepartment of Medicine, Division of Clinical Pharmacology, University of Kansas School of Medicine, Kansas City, Kansas, USA

Correspondence to Kenneth W. Grasing, MD, Substance Abuse Research Laboratory, 151, Kansas City Veterans Affairs Medical Center, 4801 Linwood Boulevard, Kansas City, MO 64128, USA E-mail: kgrasing@kumc.edu

Received December 9, 2017

Accepted November 23, 2018

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