GABA(A) receptors in the ventral tegmental area control bidirectional reward signalling between dopaminergic and non-dopaminergic neural motivational systems.
In the midbrain ventral tegmental area (VTA), both dopaminergic and nondopaminergic neural substrates mediate various behavioural reward phenomena. VTA GABAergic neurons are anatomically positioned to influence the activity of both the mesolimbic dopamine system and nondopamine efferents from the VTA. In order to examine the possible functional role of VTA GABA(A) receptors in neural reward processes, we performed discrete, bilateral microinjections of the GABA(A) receptor agonist, muscimol, or the GABA(A) receptor antagonist, bicuculline, into the VTA. Using a fully counterbalanced, unbiased conditioned place-preference paradigm, we demonstrate that activation of VTA GABA(A) receptors, with the GABA(A) receptor agonist muscimol (5--50 ng/microL), or inhibition of VTA GABA(A) receptors, with the GABA(A) receptor antagonist bicuculline (5--50 ng/microL), both produce robust rewarding effects. Furthermore, these rewarding effects can be pharmacologically dissociated: blockade of dopamine receptors with a dopamine receptor antagonist, alpha-flupenthixol (0.8 mg/kg; i.p.), or concurrent activation of VTA GABA(B) receptors with a GABA(B) receptor agonist, baclofen (70 ng/microL), blocked the rewarding properties of the GABA(A) receptor agonist, but had no effect on the rewarding properties of the GABA(A) receptor antagonist. These results suggest that, within the VTA, a single GABA(A) receptor substrate controls bidirectional reward signalling between dopaminergic and nondopaminergic brain reward systems.
Laviolette
S R
SR
Neurobiology Research Group, Department of Anatomy & Cell Biology, 1 King's College Circle, University of Toronto, Toronto, Canada, M5S 1A8. stevelaviolette@hotmail.com
van der Kooy
D
D
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004347:Drug Interactions / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D008297:Male; D009042:Motivation; D009118:Muscimol / Q000494:pharmacology; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism; D012201:Reward; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018492:Dopamine Antagonists; D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D004298:Dopamine; D001640:Bicuculline