The tipsy terminal: presynaptic effects of ethanol

Pharmacol Ther. 2005 Jul;107(1):80-98. doi: 10.1016/j.pharmthera.2005.01.006. Epub 2005 Apr 13.


Considerable evidence suggests that the synapse is the most sensitive CNS element for ethanol effects. Although most alcohol research has focussed on the postsynaptic sites of ethanol action, especially regarding interactions with the glutamatergic and GABAergic receptors, few such studies have directly addressed the possible presynaptic loci of ethanol action, and even fewer describe effects on synaptic terminals. Nonetheless, there is burgeoning evidence that presynaptic terminals play a major role in ethanol effects. The methods used to verify such ethanol actions range from electrophysiological analysis of paired-pulse facilitation (PPF) and spontaneous and miniature synaptic potentials to direct recording of ion channel activity and transmitter/messenger release from acutely isolated synaptic terminals, and microscopic observation of vesicular release, with a focus predominantly on GABAergic, glutamatergic, and peptidergic synapses. The combined data suggest that acute ethanol administration can both increase and decrease the release of these transmitters from synaptic terminals, and more recent results suggest that prolonged or chronic ethanol treatment (CET) can also alter the function of presynaptic terminals. These new findings suggest that future analyses of synaptic effects of ethanol should attempt to ascertain the role of presynaptic terminals and their involvement in alcohol's behavioral actions. Other future directions should include an assessment of ethanol's effects on presynaptic signal transduction linkages and on the molecular machinery of transmitter release and exocytosis in general. Such studies could lead to the formulation of new treatment strategies for alcohol intoxication, alcohol abuse, and alcoholism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Central Nervous System Depressants / pharmacology*
  • Ethanol / pharmacology*
  • Glutamates* / drug effects
  • Glutamates* / metabolism
  • Glutamates* / physiology
  • Humans
  • Presynaptic Terminals / drug effects*
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • gamma-Aminobutyric Acid* / drug effects
  • gamma-Aminobutyric Acid* / metabolism
  • gamma-Aminobutyric Acid* / physiology


  • Central Nervous System Depressants
  • Glutamates
  • Ethanol
  • gamma-Aminobutyric Acid