Resistance to ethanol sensitization is associated with increased NMDA receptor binding in specific brain areas.
Co-administration of N-methyl-D-aspartate (NMDA) receptor antagonists is known to block the development of behavioral sensitization to ethanol and other psychostimulants. Since ethanol sensitization in mice does not occur uniformly in all treated animals, the present study examined the possibility that NMDA receptor binding would be selectively altered in mice susceptible to ethanol sensitization. Mice received 2.4 g/kg ethanol or saline i.p. daily for 21 days and were sacrificed 24 h later. No differences in [3H]dizocilpine ([3H](+)MK-801) binding were found between sensitized and vehicle-treated mice in any of the brain regions analyzed. However, ethanol-treated mice that did not develop sensitization showed significantly higher binding in the nucleus accumbens core (+32% and +40% compared to controls and ethanol-sensitized mice, respectively; P<0.04) and the prefrontal cortex (+15% and +22%; P<0.02). In a separate experiment, sensitization resistant mice challenged with 0.25 mg/kg (+)MK 801 showed significantly less motor activation than saline-treated or ethanol-sensitized mice. These results point to a clear association between elevated NMDA receptor binding in specific brain regions and resistance to ethanol sensitization.
Quadros
Isabel M H
IM
Psychobiology Department, Federal University of São Paulo (UNIFESP), Rua Botucatu 861, 1* andar, SP, São Paulo, Brazil.
Hipólide
Débora C
DC
Frussa-Filho
Roberto
R
De Lucca
Eliane M
EM
Nobrega
José N
JN
Souza-Formigoni
Maria Lucia O
ML
D000704:Analysis of Variance; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium
D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D000431:Ethanol; D016291:Dizocilpine Maleate