Strain differences in alcohol-induced neurochemical plasticity: a role for accumbens glutamate in alcohol intake.
BACKGROUND
Repeated alcohol administration alters nucleus accumbens (NAC) basal glutamate content and sensitizes the capacity of alcohol to increase NAC extracellular glutamate levels. However, the relevance of alcohol-induced changes in NAC glutamate for alcohol drinking behavior is under-investigated.


METHODS
To examine the relationship between genetic variance in alcohol consumption and alcohol-induced neuroadaptations within the NAC, in vivo microdialysis was conducted in the alcohol-preferring C57BL/6J (B6) and alcohol-avoiding DBA2/J (D2) mouse strains on injections 1 and 8 of repeated alcohol treatment (8 x 2 g/kg, IP). To confirm an active role for NAC glutamate in regulating alcohol drinking behavior, the glutamate reuptake inhibitor dl-threo-beta-benzyloxyaspartic acid (TBOA) (300 microM) and the Group 2 metabotropic glutamate autoreceptor agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) (50 microM) were infused into the NAC of B6 and D2 mice prior to alcohol consumption in a 4 bottle-choice test.


RESULTS
While strain differences were not apparent for NAC basal levels of dopamine, serotonin or gamma-amino butyric acid (GABA), repeated alcohol treatment elevated NAC basal glutamate content only in B6 mice. Strain differences in both the acute and the sensitized neurochemical responses to 2 g/kg alcohol were observed for all neurotransmitters examined. While the alcohol-induced rise in NAC dopamine and glutamate levels sensitized in B6 mice, a sensitization was not observed in D2 animals. Moreover, B6 mice exhibited a sensitized serotonin and GABA response to alcohol followed repeated treatment, whereas neither tolerance nor sensitization was observed in D2 animals. An intra-NAC APDC infusion reduced alcohol intake in both B6 and D2 mice by approximately 50%. In contrast, TBOA infusion elevated alcohol intake selectively in B6 mice.


CONCLUSIONS
These data indicate an active role for NAC glutamate in regulating alcohol consumption in mice and support the hypothesis that predisposition to high alcohol intake involves genetic factors that facilitate alcohol-induced adaptations in glutamate release within the NAC.
Kapasova
Zuzana
Z
Department of Psychology, University of California at Santa Barbara, Santa Barbara, California 93106-9660, USA.
Szumlinski
Karen K
KK
D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D017551:Microdialysis / Q000379:methods; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D013045:Species Specificity
D000431:Ethanol; D018698:Glutamic Acid