Tonic GABA-ergic modulation of striatal dopamine release studied by in vivo microdialysis in the freely moving rat.
GABAA and GABAB receptor agonists and antagonists were administered locally in the striatum of intact and kainic acid lesioned rats. (+/-)-Baclofen, a GABAB receptor agonist, significantly decreased the level of extracellular dopamine in the striatum of intact rats. (+/-)-Phaclofen, a GABAB receptor antagonist, increased the level of extracellular dopamine in the striatum of intact rats and to a lesser extent in the striatum after kainic acid lesion. Pregnanolone (5 beta-pregnan-3 alpha-ol-20-one), a positive allosteric modulator of the GABAA receptor, significantly decreased the level of extracellular dopamine in intact rats. (-)-Bicuculline, a GABAB receptor antagonist, increased the level of extracellular dopamine in the striatum of intact rats, but failed to increase the level of extracellular dopamine after kainic acid lesion. The release of extracellular dopamine, due to infusion of phaclofen or bicuculline, was totally suppressed by tetrodotoxin. These results support a direct influence of GABA on the dopaminergic terminals via presynaptic GABAB receptors, while the effects via the GABAA receptor seem to be postsynaptic and mediated by striatal interneurons or the striatonigral feedback loop.
Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Belgium.
I
I
Smolders
N
N
De Klippel
S
S
Sarre
G
G
Ebinger
Y
Y
Michotte
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005246:Feedback / Q000187:drug effects; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D006719:Homovanillic Acid / Q000378:metabolism; D007395:Interneurons / Q000187:drug effects; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018690:Excitatory Amino Acid Agonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D015102:3,4-Dihydroxyphenylacetic Acid; D005680:gamma-Aminobutyric Acid; D007608:Kainic Acid; D004298:Dopamine; D006719:Homovanillic Acid