Self-administration of the GABAA antagonist bicuculline into the ventral tegmental area in mice: dependence on D2 dopaminergic mechanisms.
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.
David
V
V
Laboratoire de Neurosciences Comportementales et Cognitives, Talence, France.
Durkin
T P
TP
Cazala
P
P
D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007267:Injections; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D012646:Self Administration; D013469:Sulpiride / Q000494:pharmacology; D017557:Ventral Tegmental Area
D018492:Dopamine Antagonists; D018756:GABA Antagonists; D017448:Receptors, Dopamine D2; D013469:Sulpiride; D001640:Bicuculline