Abstract
Withdrawal from alcohol leads to a negative emotional state including an increase of anxiety, hyperirritability or depressed mood. The withdrawal-induced anxiety has been reported to be a risk factor for relapse [Lucht et al., Eur Addict Res, 2002]. Strong evidence indicates that enkephalins, endogenous opioid peptides with delta-opioid receptors (DORs) affinity, reveal anxiolytic-like effects [Perine et al., Br J Pharmacol, 2006] and reduce withdrawal-induced anxietylike behavior in the ethanol dependent rats [van Rijn et al., J Pharmacol Exp Ther, 2010]. A cyclic analog of enkephalin, cyclo[N ,N -carbonyl-D-Lys , Dap ] enkephalinamide (cUENK6) showed predominant affinity to MORs and, to a lesser extent to DORs in vitro [Pawlak et al., J Pept Sci, 2001]. The aim of the present study was to determine whether cUENK6 could affect an anxiety-like behavior measured during withdrawal from chronic ethanol administration in male Wistar rats. Ethanol dependence was induced according to the previously established method [Kotlinska and Bochenski, Eur J Pharmacol, 2008]. Our study indicated that ethanol decreased the time spent by rats in the open arms. This effect was reversed by intracerebroventricular (icv) administration of cUENK6 (0.0625, 0.125 and 0.25 nmol) at the doses of 0.0625 and 0.25 nmol. Our study suggests that MORs could participate in an anxiety-like behavior during withdrawal from chronic ethanol administration.
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