Novel uncompetitive N-methyl-D-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 - PubMed (original) (raw)

. 2000 Feb;292(2):545-52.

Affiliations

PMID: 10640291

Novel uncompetitive N-methyl-D-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

S M Hölter et al. J Pharmacol Exp Ther. 2000 Feb.

Abstract

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 uncompetitive N-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.

PubMed Disclaimer

Cited by

Do specific NMDA receptor subunits act as gateways for addictive behaviors?
Hopf FW. Hopf FW. Genes Brain Behav. 2017 Jan;16(1):118-138. doi: 10.1111/gbb.12348. Epub 2016 Nov 18. Genes Brain Behav. 2017. PMID: 27706932 Free PMC article. Review.
The influence of drug class on reward in substance use disorders.
Jones JD, Arout CA, Luba R, Murugesan D, Madera G, Gorsuch L, Schusterman R, Martinez S. Jones JD, et al. Pharmacol Biochem Behav. 2024 Jul;240:173771. doi: 10.1016/j.pbb.2024.173771. Epub 2024 Apr 24. Pharmacol Biochem Behav. 2024. PMID: 38670466 Review.
Acute effects of memantine in combination with alcohol in moderate drinkers.
Bisaga A, Evans SM. Bisaga A, et al. Psychopharmacology (Berl). 2004 Feb;172(1):16-24. doi: 10.1007/s00213-003-1617-5. Epub 2003 Oct 3. Psychopharmacology (Berl). 2004. PMID: 14530901 Clinical Trial.
Antagonism of glutamatergic NMDA and mGluR5 receptors decreases consumption of food in baboon model of binge-eating disorder.
Bisaga A, Danysz W, Foltin RW. Bisaga A, et al. Eur Neuropsychopharmacol. 2008 Nov;18(11):794-802. doi: 10.1016/j.euroneuro.2008.05.004. Epub 2008 Jun 24. Eur Neuropsychopharmacol. 2008. PMID: 18573641 Free PMC article.
Glutamate Receptors within the Mesolimbic Dopamine System Mediate Alcohol Relapse Behavior.
Eisenhardt M, Leixner S, Luján R, Spanagel R, Bilbao A. Eisenhardt M, et al. J Neurosci. 2015 Nov 25;35(47):15523-38. doi: 10.1523/JNEUROSCI.2970-15.2015. J Neurosci. 2015. PMID: 26609150 Free PMC article.

Novel uncompetitive N-methyl-D-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 - PubMed (original) (raw)