RT Journal Article
SR Electronic
T1 Novel Uncompetitive<em>N</em>-Methyl-<span class="sc">d</span>-Aspartate (NMDA)-Receptor Antagonist MRZ 2/579 Suppresses Ethanol Intake in Long-Term Ethanol-Experienced Rats and Generalizes to Ethanol Cue in Drug Discrimination Procedure
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 545
OP 552
VO 292
IS 2
A1 Sabine M. Hölter
A1 Wojciech Danysz
A1 Rainer Spanagel
YR 2000
UL http://jpet.aspetjournals.org/content/292/2/545.abstract
AB Previous findings suggested that drugs modulating glutamatergic neurotransmission could be useful in the treatment of alcohol dependence. This study examined the effects of chronic and acute treatment with MRZ 2/579 (1-amino-1,3,3,5,5-pentamethyl-cyclohexane hydrochloride), a novel uncompetitiveN-methyl-d-aspartate receptor antagonist, on voluntary ethanol intake in long-term ethanol-experienced rats. Rats were implanted with mini-osmotic pumps delivering either 9.6 mg/day MRZ 2/579 or vehicle, and the effects of treatment on the alcohol deprivation effect (ADE) were studied in a four-bottle home cage-drinking paradigm. The same rats were tested for a second ADE 3 weeks later in the absence of the drug. In a second experiment long-term ethanol-experienced rats trained in an operant free-choice ethanol self-administration paradigm with concurrent water received acute MRZ 2/579 treatment (0–4 mg/kg i.p.) before a 23-h session either during basal drinking or during the ADE. In an additional experiment, MRZ 2/579 (0.5–4 mg/kg i.p.) was tested for generalization to the ethanol cue in a drug discrimination procedure. Chronic MRZ 2/579 treatment selectively abolished the increased ethanol intake during the ADE. This effect depended on the presence of the drug. Acute MRZ 2/579 treatment (2 and 4 mg/kg) had a short-lasting reductive effect on lever pressing for ethanol, but not for water, both during the ADE and basal drinking. MRZ 2/579 dose dependently generalized to the ethanol cue in the drug discrimination experiment. It is concluded that MRZ 2/579 might exert its reducing effect on ethanol intake by substituting for some of the stimulus properties of ethanol. The American Society for Pharmacology and Experimental Therapeutics