Inhibition of glycine receptor function of native neurons by aliphatic n-alcohols

Br J Pharmacol. 2002 Jun;136(4):629-35. doi: 10.1038/sj.bjp.0704775.

Abstract

The inhibitory effects of n-alcohols (methanol to dodecanol) on glycine-activated currents were studied in neurons freshly dissociated from the ventral tegmental area of neonatal rats using whole-cell patch-clamp recording technique. Ethanol enhanced and depressed glycine-activated currents in 35% and 45%, respectively, of neurons of ventral tegmental area of neonatal rats. In this report, we extended our focus of ethanol-induced inhibition of glycine currents to other straight-chain alcohols. Aliphatic n-alcohols, which have carbon numbers less than nine, suppressed glycine currents in 45% (71/158) of the neurons. All results from this study are obtained from the 45% of cells displaying inhibition; the other 55% of the neurons were not studied. Alcohol potency increased as the number of carbon atoms increased from one to five, and was at a maximal plateau from five to nine; alcohols with 10 or more carbons did not inhibit glycine-activated currents. Thus, a 'cutoff' point in their potency for inhibition of glycine receptor function occurred at about decanol. A coapplication of dodecanol with ethanol eliminated the inhibition resulting from ethanol. Thus, dodecanol may bind to the receptor silently and compete with ethanol. These observations indicate that straight-chain n-alcohols exhibit a 'cutoff' point in their potency for inhibition of the glycine receptor function between nine and 10 carbon atoms. The inability of longer alcohols to change the activation properties of the receptors may contribute to the cutoff effect.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alcohols / pharmacology*
  • Animals
  • Animals, Newborn
  • In Vitro Techniques
  • Neurons / drug effects*
  • Neurons / physiology
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glycine / drug effects*
  • Receptors, Glycine / physiology
  • Ventral Tegmental Area / cytology

Substances

  • Alcohols
  • Receptors, Glycine