Nucleus accumbens dopamine release modulation by mesolimbic GABAA receptors-an in vivo electrochemical study

Brain Res. 1998 Jul 6;798(1-2):156-65. doi: 10.1016/s0006-8993(98)00406-5.


The role of GABA receptors in regulating the mesolimbic dopamine (DA) system and drug reinforced behaviors has not been well characterized. Using fast-cyclic voltammetry, the effects of specific GABA receptor modulation on DA release in the nucleus accumbens (NAcc) and heroin self-administration (SA) behavior was investigated. The GABAA agonist muscimol, administered either intravenously or directly into the ventral tegmental area (VTA), significantly increased DA release in the NAcc in 7 of the 10 rats tested. DA release decreased in the remaining three rats; both effects were blocked by pretreatment with the GABAA receptor antagonist bicuculline. In contrast, the GABAB agonist baclofen decreased, while 2-OH-saclofen (a GABAB antagonist) increased DA release in the NAcc. However, when VTA GABAB receptors were previously activated or inactivated by microinjections of baclofen or 2-OH-saclofen, systemic injections of muscimol caused an inhibition of NAcc DA release. These results suggest that GABAA receptors may be co-localized on both DA neurons and non-DA (GABAergic) interneurons in the VTA, with the effects of GABAA determined by the net effect of both direct inhibition and indirect disinhibition of DA neurons. Finally, although a DA releaser, muscimol was neither self-administered in drug naive rats, nor did it substitute for heroin in rats previously trained to self-administer heroin, suggesting that GABAA receptors appear to play a complex role in mediating drug reinforcement, depending upon the dynamic functional state of GABAA receptors on both tegmental DA and non-DA neurons.

Publication types

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

MeSH terms

  • Animals
  • Baclofen / analogs & derivatives
  • Baclofen / pharmacology
  • Dopamine / metabolism*
  • Electrochemistry
  • GABA Antagonists / pharmacology
  • GABA-A Receptor Agonists
  • GABA-B Receptor Agonists
  • Limbic System / metabolism*
  • Male
  • Muscimol / administration & dosage
  • Muscimol / pharmacology
  • Nucleus Accumbens / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Receptors, GABA-A / physiology*
  • Self Administration


  • GABA Antagonists
  • GABA-A Receptor Agonists
  • GABA-B Receptor Agonists
  • Receptors, GABA-A
  • Muscimol
  • Baclofen
  • Dopamine
  • 2-hydroxysaclofen