Self-administration of the GABAA antagonist bicuculline into the ventral tegmental area in mice: dependence on D2 dopaminergic mechanisms

Psychopharmacology (Berl). 1997 Mar;130(2):85-90. doi: 10.1007/s002130050214.

Abstract

BALB/c mice were unilaterally implanted with a guide cannula, the tip of which was positioned 1.5 mm above the ventral tegmental area (VTA). On each day of the experimental period, a stainless steel injection cannula was inserted into the VTA in order to study the eventual self-administration of a low dose (1.5 ng/50 nl) of bicuculline, a GABAA-antagonist, using a spatial discrimination task in a Y maze. Mice rapidly discriminated between the arm enabling a micro-injection of bicuculline and the neutral arm of the maze, and robust self-administration of this GABAergic antagonist was observed. Once this self-administration response for bicuculline had been fully acquired, the systemic injection of the dopaminergic D2 antagonist sulpiride (50 mg/kg), 30 min before the test, produced a rapid extinction of the self-administration response. Moreover, if this same sulpiride pretreatment was given during the initial acquisition period mice did not discriminate between the two arms of the Y-maze. These data demonstrate the dopamine D2 dependence of this bicuculline self-administration behavior, and confirm that GABAergic interneurons and/or inputs normally transynaptically inhibit neuronal activity in the mesocorticolimbic dopamine system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bicuculline / administration & dosage
  • Bicuculline / pharmacology*
  • Conditioning, Operant / drug effects
  • Dopamine Antagonists / pharmacology
  • GABA Antagonists / administration & dosage
  • GABA Antagonists / pharmacology*
  • Injections
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Dopamine D2 / drug effects*
  • Self Administration
  • Sulpiride / pharmacology
  • Ventral Tegmental Area

Substances

  • Dopamine Antagonists
  • GABA Antagonists
  • Receptors, Dopamine D2
  • Sulpiride
  • Bicuculline