Alcohol
  • Identification of ?-isoform of GABAA receptor, which has high-affinity binding site for alcohol (i.e., alcohol receptor?).

  • Physiologically relevant doses of alcohol (10–50 mM) shown to: enhance Cl- flux mediated by the GABAA-benzodiazepine receptor complex; inhibit Ca++ flux mediated by the NMDA-glutamate receptor system; and enhance Na+ and K+ flux mediated by the 5-HT3 receptor.

  • Acute alcohol effects on NMDA-glutamate receptor and downstream actions of increased intracellular Ca++ on nitric oxide production implicated in acute tolerance development.

  • Chronic alcohol down-regulation of GABAA-benzodiazepine receptor complex and up-regulation of NMDA-glutamate receptor complex implicated in chronic tolerance development.

  • Low-to-moderate doses of alcohol increase the release of endogenous opioid peptides that may contribute to its effect on brain reward systems.

  • Alcohol's effect on firing of dopamine neurons in the ventral tegmental area (VTA) and increases in extracellular dopamine in the nucleus accumbens (NAc) may also contribute to the positive reinforcing effects of alcohol.

  • Serotonin, glutamate, opioid, and GABAergic neurons may modulate alcohol's reinforcing effects or mediate negative reinforcement from alcohol withdrawal.

ANIMAL MODELS, EXPERIMENTAL THERAPEUTICS, AND GENETICS

General Issues
  • Expanded research into the neurobiological basis and behavioral mechanisms for ''craving" and reinitiation of drug use.

  • Use of animal self-administration models, place-preference testing, drug discrimination, and other behavioral models in conjunction with:

    • in vitro and in vivo neurochemistry (microdialysis, neurotransmitter-selective electrodes, autoradiography),

    • brain imaging,

    • new strains of drug-responsive and nonresponsive animals,

    • quantitative trait loci (QTL) gene mapping, and

    • molecular biology (transgenic, gene knockout, antisense DNA).



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement