Influence of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference in rats

• Published in: Behavioural brain research 2014-07, Vol.268, p.169-176
• Main Authors: Gawel, Kinga, Labuz, Krzysztof, Jenda, Malgorzata, Silberring, Jerzy, Kotlinska, Jolanta H.
• Format: Article
• Language: English
• Subjects: Analgesics; Animals; Biological and medical sciences; Cholinesterase Inhibitors - pharmacology; Conditioned place preference; Conditioning (Psychology) - drug effects; Donepezil; Drug-Seeking Behavior - drug effects; Fundamental and applied biological sciences. Psychology; Indans - pharmacology; Male; Mecamylamine - pharmacology; Medical sciences; Morphine; Morphine - pharmacology; Motor Activity - drug effects; Muscarinic Antagonists - pharmacology; Narcotics - pharmacology; Neuropharmacology; Nicotinic Antagonists - pharmacology; Pharmacology. Drug treatments; Phenylcarbamates - pharmacology; Piperidines - pharmacology; Rats, Wistar; Rivastigmine; Scopolamine Hydrobromide - pharmacology; Space Perception - drug effects; Vertebrates: nervous system and sense organs
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2014.04.019

•Morphine-induced rewarding effects in conditioned place preference paradigm.•Morphine effects were more effectively attenuated by rivastigmine than by donepezil.•Mecamylamine reversed donepezil and rivastigmine effects on morphine reinstatement.•Nicotinic acetylcholine receptors are involved in morphine seeking after abstinence.•Donepezil and rivastigmine may be useful in therapy of morphine dependence. 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 (5mg/kg, i.p.). Donepezil (0.5, 1, and 3mg/kg, i.p.) or rivastigmine (0.03, 0.5, and 1mg/kg, i.p.) were given 20min before morphine during conditioning phase and 20min 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 (1mg/kg) and rivastigmine (0.5mg/kg) attenuated the morphine CPP reinstated by priming injection of 5mg/kg morphine. These properties of both cholinesterase inhibitors were reversed by mecamylamine (3mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist but not scopolamine (0.5mg/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.