Acquisition and reinstatement of ethanol-induced conditioned place preference in rats: Effects of the cholinesterase inhibitors donepezil and rivastigmine.
The present study examined the influence of the cholinesterase inhibitors donepezil (a selective inhibitor of acetylcholinesterase) and rivastigmine (also an inhibitor of butyrylcholinesterase) on the acquisition and reinstatement of ethanol-induced conditioned place preference (CPP) in rats. Before the CPP procedure, animals received a single injection of ethanol (0.5 g/kg, 10% w/v, intraperitoneally [i.p.]) for 15 days. The ethanol-induced CPP (biased method) was developed by four injections of ethanol (0.5 g/kg, 10% w/v, i.p.) every second day. Control rats received saline instead of ethanol. Donepezil (0.5, 1 or 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5 or 1 mg/kg, i.p.) were administered before ethanol during conditioning or before the reinstatement of ethanol-induced CPP. The cholinesterase inhibitors were equally effective in increasing (dose dependently) the acquisition of ethanol-induced CPP. Furthermore, priming injections of both inhibitors reinstated (cross-reinstatement) the ethanol-induced CPP with similar efficacy. These effects of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist, but not by scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. Thus, our results show that the cholinergic system is involved in the reinforcing properties of ethanol, and nicotinic acetylcholine receptors play an important role in the relapse to ethanol-seeking behaviour.
Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland.
Kinga
K
Gawel
Sahlgrenska University Hospital, Göteborg, Sweden.
Krzysztof
K
Labuz
Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland.
Ewa
E
Gibula-Bruzda
Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland.
Malgorzata
M
Jenda
Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland.
Marta
M
Marszalek-Grabska
Department of Biochemistry and Neurobiology, AGH University of Science and Technology, Krakow, Poland.
Jerzy
J
Silberring
Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland jolanta.kotlinska@umlub.pl.
Jolanta H
JH
Kotlinska
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D000077265:Donepezil; D000431:Ethanol / Q000009:adverse effects*; D007189:Indans / Q000494:pharmacology*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism; D012054:Reinforcement, Psychology; D000068836:Rivastigmine / Q000494:pharmacology*; D012601:Scopolamine / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D007189:Indans; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D010880:Piperidines; D011978:Receptors, Nicotinic; D000431:Ethanol; D008464:Mecamylamine; D000077265:Donepezil; D012601:Scopolamine; D000068836:Rivastigmine
Conditioned place preference; acquisition; cholinesterase inhibitors; donepezil; ethanol; reinstatement; rivastigmine