Involvement of non-exocytotic mechanisms in ethanol-induced in vivo dopamine release: comparisons with cocaine

Eur J Pharmacol. 2003 Sep 5;477(1):37-44. doi: 10.1016/j.ejphar.2003.08.008.

Abstract

In order to determine whether a non-exocytotic mechanism was involved in ethanol-induced in vivo dopamine release in the nucleus accumbens, extracellular dopamine concentrations were measured via intracerebral microdialysis in freely moving Sprague-Dawley rats. Effects of ethanol on dopamine release in the nucleus accumbens were compared with those by cocaine, a drug that increases synaptic dopamine by a mechanism, which depends on neuronal activity and involves an exocytotic process. Administration of ethanol (80 mM) or cocaine (10 microM) via a dialysis probe increased extracellular dopamine concentrations in the nucleus accumbens. Pretreatments with tetrodotoxin (2 microM) or Ca2+ withdrawal did not block the ability of ethanol to increase nucleus accumbens dopamine. The blockade of dopamine autoreceptors by local infusion of sulpiride did not significantly alter the effect of ethanol on nucleus accumbens dopamine either. As opposed to ethanol, however, cocaine-induced increases in nucleus accumbens dopamine were sensitive to tetrodotoxin or Ca2+ omission. In addition, pretreatments with sulpiride significantly potentiated the effect of cocaine on extracellular dopamine concentrations. These differences in responses to tetrodotoxin, Ca2+ withdrawal and inhibition of dopamine autoreceptors suggest that a non-exocytotic mechanism may be involved in dopamine release in the nucleus accumbens evoked by focally applied ethanol.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cocaine / pharmacology*
  • Dopamine / biosynthesis*
  • Dopamine D2 Receptor Antagonists
  • Ethanol / pharmacology*
  • Extracellular Space / drug effects
  • Male
  • Microdialysis
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Perfusion
  • Rats
  • Rats, Sprague-Dawley
  • Sulpiride / pharmacology
  • Tetrodotoxin / pharmacology
  • Time Factors

Substances

  • Dopamine D2 Receptor Antagonists
  • Ethanol
  • Tetrodotoxin
  • Sulpiride
  • Cocaine
  • Calcium
  • Dopamine