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 psycho stimulants. 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 It later. No differences in [H-3]dizoeilpine ([H-3]( -)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. (C) 2002 Elsevier Science B.V. All rights reserved.