The goal of this proposal is to investigate the inhibitory effects of ethanol on N-methyl-D-aspartate-evoked neuronal activity in vivo. This proposal pursues recent in vivo studies in our laboratory showing that ethanol, throughout a wide range of behaviorally relevant doses, inhibits the excitatory effects of N-methyl-D-aspartate (NMDA) in only a subset of neurons in the medial septum. This finding indicates that there exist both ethanol-sensitive and ethanol-insensitive NMDA-activated neurons in the medial septum. This proposal will test implications of the hypothesis that there exist both ethanol-sensitive and ethanol-insensitive NMDA activated neurons in brain by investigating 1) whether ethanol specifically inhibits medial septa] neuronal activity evoked by agonists of the NMDA receptor subtype of the glutamate receptor or, if not, whether differences in ethanol sensitivity occur in neurons activated by agonists of kainate and quisqualate glutamate receptor subtypes, 2) whether differences in ethanol sensitivity of NMDA-activated medial septa] neurons are due to local effects or effects of neural circuits, and 3) whether ethanol-sensitive and ethanol-insensitive NMDA-activated neurons exist at selected brain sites other than the medial septum and, if so, whether the proportion of neurons sensitive to ethanol varies systematically at these sites depending on NMDA receptor subpopulation distributions. This third approach permits testing of the hypothesis that the lack of inhibition by ethanol of responses to NMDA in some medial septal neurons is due to the presence of two types of NMDA receptors, one ethanol-sensitive, the other ethanol-insensitive.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AA009079-04
Application #
2045283
Study Section
Biochemistry, Physiology and Medicine Subcommittee (ALCB)
Project Start
1993-08-01
Project End
1996-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Miami University Oxford
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
041065129
City
Oxford
State
OH
Country
United States
Zip Code
45056
Matthews, D B; Simson, P E (1998) Prenatal exposure to ethanol disrupts spatial memory: effect of the training-testing delay period. Physiol Behav 64:63-7
White, A M; Simson, P E; Best, P J (1997) Comparison between the effects of ethanol and diazepam on spatial working memory in the rat. Psychopharmacology (Berl) 133:256-61
Matthews, D B; Simson, P E; Best, P J (1996) Ethanol alters spatial processing of hippocampal place cells: a mechanism for impaired navigation when intoxicated. Alcohol Clin Exp Res 20:404-7
Yang, X; Criswell, H E; Simson, P et al. (1996) Evidence for a selective effect of ethanol on N-methyl-d-aspartate responses: ethanol affects a subtype of the ifenprodil-sensitive N-methyl-d-aspartate receptors. J Pharmacol Exp Ther 278:114-24
Criswell, H E; Simson, P E; Knapp, D J et al. (1995) Effect of zolpidem on gamma-aminobutyric acid (GABA)-induced inhibition predicts the interaction of ethanol with GABA on individual neurons in several rat brain regions. J Pharmacol Exp Ther 273:526-36
Matthews, D B; Simson, P E; Best, P J (1995) Acute ethanol impairs spatial memory but not stimulus/response memory in the rat. Alcohol Clin Exp Res 19:902-9
Simson, P E; Criswell, H E; Breese, G R (1993) Inhibition of NMDA-evoked electrophysiological activity by ethanol in selected brain regions: evidence for ethanol-sensitive and ethanol-insensitive NMDA-evoked responses. Brain Res 607:9-16
Criswell, H E; Simson, P E; Duncan, G E et al. (1993) Molecular basis for regionally specific action of ethanol on gamma-aminobutyric acidA receptors: generalization to other ligand-gated ion channels. J Pharmacol Exp Ther 267:522-37