title: The influence of the new enkephalin derivative, cyclo[N(ε),N(β)-carbonyl-d-Lys(2),Dap(5)] enkephalinamide (cUENK6), on reinstatement of ethanol-induced conditioned place preference in rats.
abstract: The aim of the present study was to determine whether a new cyclic analog of enkephalin, cyclo[N(ε),N(β)-carbonyl-d-Lys(2),Dap(5)] enkephalinamide (cUENK6), a preferential μ-(MORs), and, to a lower extent, a δ-opioid receptor (DORs) agonist in vitro, could reinstate ethanol-induced conditioned place preference (CPP). In our work, male Wistar rats were first conditioned either with ethanol (10% w/v, 0.5g/kg, intraperitoneally (i.p.)) or 0.9% NaCl in a biased CPP procedure. The intracerebroventricular (i.c.v.) administration of DORs antagonist (naltrindole, 2.5 and 5nmol) or MORs antagonist (β-funaltrexamine, 5 and 10nmol), but not the κ opioid receptor (KORs) antagonist (norbinaltorphimine, 5 and 10nmol) was then administered and inhibited the expression of ethanol-induced CPP. After the extinction session, i.c.v. administration of cUENK6 at the dose of 0.125, 0.25 and 0.5nmol occurred, and was found to reinstate the ethanol-induced CPP similar to that of the priming injection of ethanol. However, the reinstated effect of cUENK6 (0.25nmol) was strongly abolished by administration of naltrindole and, to lesser extent, by β-funaltrexamine. Furthermore, the preferential MORs agonist-morphine (13nmol, i.c.v.) and the DORs agonist-[Leu(5)]-enkephalin (2.7 and 5.4nmol, i.c.v.) also reinstated the ethanol-induced CPP. cUENK6 given alone at the dose of 0.25nmol before the testing phase had no effect in animals that received 0.9% NaCl during the conditioning phase and also did not influence their locomotor activity. These data suggest that the effects of cUENK6 did not have an impact on the results obtained in the reinstatement procedure of CPP. Overall, the data support the idea that both MORs and DORs are normally involved in the expression and reinstatement of ethanol conditioned seeking behavior - as indexed by CPP in rats.
authors: Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland. Electronic address: ewa.gibulabruzda@umlub.pl.
authors: Ewa
authors: E
authors: Gibula-Bruzda
authors: Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland.
authors: Marta
authors: M
authors: Marszalek-Grabska
authors: Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland.
authors: Kinga
authors: K
authors: Gawel
authors: Laboratory of Peptides, Department of Chemistry, University of Warsaw, Warsaw, Poland.
authors: Ewa
authors: E
authors: Witkowska
authors: Laboratory of Peptides, Department of Chemistry, University of Warsaw, Warsaw, Poland.
authors: Jan
authors: J
authors: Izdebski
authors: Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland.
authors: Jolanta H
authors: JH
authors: Kotlinska
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004745:Enkephalins / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009292:Narcotic Antagonists / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology
chemical_list: D002492:Central Nervous System Depressants; D004745:Enkephalins; D009292:Narcotic Antagonists; D018377:Neurotransmitter Agents; C543922:enkephalinamide, cyclo(Nepsilon,Nbeta-carbonyl-Lys(2)-Dap(5))-; D000431:Ethanol
keywords: Conditioned place preference; Ethanol; Opioid antagonists; Reinstatement; cUENK6