The role of GABA receptors in the control of nigrostriatal dopaminergic neurons: dual-probe microdialysis study in awake rats.
A microdialysis probe implanted into the substantia nigra was used to infuse gamma-aminobutyric acid-ergic (GABAergic) compounds onto cell bodies/dendrites of dopaminergic neurons, while a second microdialysis probe was used to record the extracellular concentrations of dopamine and 3,4-dihydroxy-phenylacetic acid (DOPAC) in the ipsilateral striatum. The GABAA receptor agonist muscimol (10 mumol/l) increased the release of dopamine in the ipsilateral striatum to 120% of the control values. The GABAB receptor agonist, (Z)-3[(aminoiminomethyl)-thiol]-prop-2- enoic acid (500 mumol/l), was without effect. Infusion of the GABAA receptor antagonists, bicuculline (50 mumol/l) and picrotoxin (50 mumol/l), stimulated the release of dopamine in the ipsilateral striatum to 160 and 130% of the controls, respectively. The GABAB receptor agonist, baclofen (10 and 50 mumol/l), strongly inhibited the release of striatal dopamine, whereas infusion of the GABAB receptor antagonist, 2-hydroxy-saclofen (100 mumol/l), was without effect. The results indicate that, in the substantia nigra, GABAA as well as GABAB receptors participate in controlling the activity of dopaminergic neurons.
Santiago
M
M
Department of Biochemistry, Faculty of Pharmacy, University of Seville, Spain.
Westerink
B H
BH
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000179:Acrylates / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*
D015102:3,4-Dihydroxyphenylacetic Acid; D000179:Acrylates; D001418:Baclofen; D001640:Bicuculline; D004298:Dopamine; D009118:Muscimol; D010852:Picrotoxin; D011963:Receptors, GABA-A; C058552:3-((aminoiminomethyl)thio)-2-propenoic acid; C057491:2-hydroxysaclofen