Effects of Repeated Ethanol Exposures on NMDA Receptor Expression and Locomotor Sensitization in Mice Expressing Ethanol Resistant NMDA Receptors.

摘要: Evidence from a large number of preclinical studies suggests that chronic exposure to drugs abuse such as psychostimulants or ethanol induces changes in glutamatergic transmission key brain areas associated with reward and control behavior. These include alterations the expression ionotropic glutamate receptors including N-methyl-D-aspartate (NMDAR) are important for regulating neuronal activity synaptic plasticity. NMDA inhibited by reductions NMDA-mediated signaling thought trigger homestatic responses limit ethanol’s effects on transmission. Following repeated exposures ethanol, these homeostatic may become unstable leading an altered state contributes escalations drinking cognitive deficits observed alcohol-dependent subjects. An unanswered question is whether ethanol-induced NMDAR modulated intrinsic sensitivity receptor ethanol. In this study, we examined subunit cortical (orbitofrontal, medial prefrontal), striatal (dorsal ventral striatum) limbic hippocampus, basolateral amygdala) mice genetically modified express ethanol-resistant (F639A mice). have been previously shown drink more than their wild-type counterparts behavioral certain actions long-term voluntary drinking, F639A showed elevations GluN2A but not GluN1 GluN2B compared mice. Mice treated injections (2-3.5 g/kg; i.p.) varied complex manner genotype, region, type protocol all contributing response. mice, enhanced motor following was differences across regions be involved drug sensitization. Overall, while results study suggest NMDARs reduced favor development locomotor sensitization, they also show sole determinant underlying