title: Influence of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference in rats.
abstract: The influence of systemic administration of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference (CPP) was examined in rats. Additionally, this study aimed to compare the effects of donepezil, which selectively inhibits acetylcholinesterase, and rivastigmine, which inhibits both acetylcholinesterase and butyrylcholinesterase on morphine reward. Morphine-induced CPP (unbiased method) was induced by four injections of morphine (5 mg/kg, i.p.). Donepezil (0.5, 1, and 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5, and 1 mg/kg, i.p.) were given 20 min before morphine during conditioning phase and 20 min before the expression or reinstatement of morphine-induced CPP. Our results indicated that both inhibitors of cholinesterase attenuated the acquisition and expression of morphine CPP. The results were more significant after rivastigmine due to a broader inhibitory spectrum of this drug. Moreover, donepezil (1 mg/kg) and rivastigmine (0.5 mg/kg) attenuated the morphine CPP reinstated by priming injection of 5mg/kg morphine. These properties of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist but not scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. All effects of cholinesterase inhibitors were observed at the doses that had no effects on locomotor activity of animals. Our results suggest beneficial role of cholinesterase inhibitors in reduction of morphine reward and morphine-induced seeking behavior. Finally, we found that the efficacy of cholinesterase inhibitors in attenuating reinstatement of morphine CPP provoked by priming injection may be due to stimulation of nicotinic acetylcholine receptors.
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4a, 20-093 Lublin, Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Gawel
authors.affiliation: Addiction Outpatient Clinic, The Rydygier Hospital, Zlotej Jesieni 1, 31-826 Krakow, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Labuz
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4a, 20-093 Lublin, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Jenda
authors.affiliation: Department of Biochemistry and Neurobiology, AGH University of Science and Technology, Mickiewicza 30, 30-059 Krakow, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Silberring
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4a, 20-093 Lublin, Poland. Electronic address: jolka.kotlinska@umlub.pl.
authors.forename: Jolanta H
authors.initials: JH
authors.lastname: Kotlinska
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D000077265:Donepezil; D058999:Drug-Seeking Behavior / Q000187:drug effects; D007189:Indans / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D048448:Phenylcarbamates / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017208:Rats, Wistar; D000068836:Rivastigmine; D012601:Scopolamine / Q000494:pharmacology; D013028:Space Perception / Q000187:drug effects*
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D018727:Muscarinic Antagonists; D009294:Narcotics; D018733:Nicotinic Antagonists; D048448:Phenylcarbamates; D010880:Piperidines; D008464:Mecamylamine; D009020:Morphine; D000077265:Donepezil; D012601:Scopolamine; D000068836:Rivastigmine
keywords: Conditioned place preference; Donepezil; Morphine; Rivastigmine