Sub-chronic low dose gamma-vinyl GABA (vigabatrin) inhibits cocaine-induced increases in nucleus accumbens dopamine

Psychopharmacology (Berl). 2003 Jul;168(3):339-43. doi: 10.1007/s00213-003-1446-6. Epub 2003 Apr 9.

Abstract

Rationale: gamma-Vinyl GABA (GVG) irreversibly inhibits GABA-transaminase. This non-receptor mediated inhibition requires de novo synthesis for restoration of functional GABA catabolism.

Objectives: Given its preclinical success for treating substance abuse and the increased risk of visual field defects (VFD) associated with cumulative lifetime exposure, we explored the effects of sub-chronic low dose GVG on cocaine-induced increases in nucleus accumbens (NAcc) dopamine (DA).

Methods: Using in vivo microdialysis, we compared acute exposure (450 mg/kg) to an identical sub-chronic exposure (150 mg/kg per day for 3 days), followed by 1- or 3-day washout. Finally, we examined the low dose of 150 mg/kg (50 mg/kg per day) using a similar washout period.

Results: Sub-chronic GVG exposure inhibited the effect of cocaine for 3 days, which exceeded in magnitude and duration the identical acute dose.

Conclusions: Sub-chronic low dose GVG potentiates and extends the inhibition of cocaine-induced increases in dopamine, effectively reducing cumulative exposures and the risk for VFDS.

Publication types

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

MeSH terms

  • 4-Aminobutyrate Transaminase / antagonists & inhibitors*
  • Animals
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / drug therapy*
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Male
  • Microdialysis
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Vigabatrin / administration & dosage
  • Vigabatrin / pharmacology*

Substances

  • 4-Aminobutyrate Transaminase
  • Vigabatrin
  • Cocaine
  • Dopamine