The role of the NMDA receptor in alcohol relapse: a pharmacological mapping study using the alcohol deprivation effect
Section snippets
Animals
Two-month-old male Wistar rats (from our own breeding colony at the CIMH, Mannheim, Germany) were used. All animals were housed individually in standard rat cages under a 12 h artificial light–dark cycle (lights on at 6:00 a.m.). Room temperature was kept constant (temperature: 22 ± 1 °C, humidity: 55 ± 5%). Standard laboratory rat food and water were provided ad libitum throughout the experimental period. Body weights were measured weekly. The experiments were approved by the Committee on Animal
Results
The pharmacological studies were performed at the end of the seventh alcohol deprivation phase. Following the re-introduction of alcohol solutions, all four vehicle treated groups (G1, G6, G9 and G12) showed a typical increase in alcohol consumption indicating the occurrence of an ADE. This increase was not different from that observed during the first six deprivation periods. The treatment with CGP 37849, neramexane and L-701.324 produced rather similar effects, i.e. the drug treatment caused
Discussion
In the present study, the repeated administration of the competitive NMDAR antagonist CGP37849, the NMDAR channel blocker neramexane, and the NR2B subunit selective antagonist ifenprodil, which acts at the polyamine binding site, as well as the glycine binding site antagonist L-701.324, produced a significant dose-dependent reduction of alcohol intake in long-term drinking rats during ADE. As well, IP administration of ethanol displayed a similar effect, as it completely abolished alcohol
Acknowledgements
This study was supported by a BMBF grant FKZ EB 01011300 – Individually adapted therapy of alcoholism (RS) and an EC grant QLG3-CT-2002-01048 – Identification and validation of molecular targets for pharmacological treatment of alcohol dependence (TARGALC group; RS).
References (53)
Ethanol sensitivity of NMDA receptors
Neurochemistry International
(2002)- et al.
Study on the role of glycine, strychnine-insensitive receptors (glycineB sites) in the discriminative stimulus effects of ethanol in the rat
Alcohol
(1998) - et al.
Effects of N-methyl-d-aspartate receptor antagonists on reinforced and nonreinforced responding for ethanol in rats
Alcohol
(1999) - et al.
Effects of a novel uncompetitive NMDA receptor antagonist, MRZ 2/579 on ethanol self-administration and ethanol withdrawal seizures in the rat
European Journal of Pharmacology
(2001) - et al.
Competitive NMDA receptor antagonist, CGP 40116, substitutes for the discriminative stimulus effects of ethanol
European Journal of Pharmacology
(1996) - et al.
Selective NMDA NR2B antagonists induce antinociception without motor dysfunction: correlation with restricted localisation of NR2B subunit in dorsal horn
Neuropharmacology
(1999) - et al.
NMDA receptor antagonists as analgesics: focus on the NR2B subtype
Trends in Pharmacological Sciences
(2001) - et al.
Glutamate-mediated transmission, alcohol, and alcoholism
Neurochemistry International
(2000) - et al.
Effects of NMDA antagonists on ethanol-withdrawal induced “anxiety” in the elevated plus maze
Alcohol
(1999) - et al.
Long-term voluntary ethanol drinking increases expression of NMDA receptor 2B subunits in rat frontal cortex
European Journal of Pharmacology
(2003)
Chronic acamprosate eliminates the alcohol deprivation effect while having limited effects on baseline responding for ethanol in rats
Neuropsychopharmacology
Evidence for alcohol anti-craving properties of memantine
European Journal of Pharmacology
Modulation of channel function by polyamines
Trends in Pharmacological Sciences
The NMDA/glycine receptor antagonist, L-701.324, produces discriminative stimuli similar to those of ethanol
European Journal of Pharmacology
N-methyl-d-aspartate glutamate receptors and alcoholism: reward, dependence, treatment, and vulnerability
Pharmacology & Therapeutics
Ifenprodil influences changes in mouse behaviour related to acute and chronic ethanol administration
European Journal of Pharmacology
NR2B subunit selective NMDA antagonists inhibit neurotoxic effect of alcohol-withdrawal in primary cultures of rat cortical neurones
Neurochemistry International
NMDA receptors as targets for drug action in neuropathic pain
European Journal of Pharmacology
Anticonflict effects of a competitive NMDA receptor antagonist and a partial agonist at strychnine-insensitive glycine receptors
Pharmacology Biochemistry and Behavior
The anti-craving compound acamprosate acts as a weak NMDA-receptor antagonist, but modulates NMDA-receptor subunit expression similar to memantine and MK-801
Neuropharmacology
Effects of 5-HT(3) receptor antagonists on daily alcohol intake under acquisition, maintenance, and relapse conditions in alcohol-preferring (P) rats
Alcohol
Ethanol inhibition of N-methyl-d-aspartate receptors is reduced by site-directed mutagenesis of a transmembrane domain phenylalanine residue
Journal of Biological Chemistry
The alcohol deprivation effect in hybrid mice
Drug and Alcohol Dependence
Anti-relapse properties of IDN 5082, a standardized extract of Salvia miltiorrhiza, in alcohol-preferring rats
Journal of Ethnopharmacology
Alcohol addiction research: from animal models to clinics
Best Practice and Research Clinical GA
Acamprosate and alcohol: I. Effects on alcohol intake following alcohol deprivation in the rat
European Journal of Pharmacology
Cited by (121)
Açaí juice (Euterpe oleraceae) prevents ethanol-induced motor impairments in adolescent female rats
2023, Journal of Functional FoodsFACTORS CONTRIBUTING TO THE ESCALATION OF ALCOHOL CONSUMPTION
2022, Neuroscience and Biobehavioral ReviewsAlcohol: Neurobiology of Addiction
2021, Alcohol: Neurobiology of AddictionNicotinic cholinergic mechanisms in alcohol abuse and dependence
2019, Neuroscience of Alcohol: Mechanisms and Treatment