Tonic inhibition of striatal dopamine transmission: effects of benzodiazepine and GABAA receptor antagonists on extracellular dopamine levels.
At present, it is unclear whether ligands which bind at the benzodiazepine/GABA receptor complex play a tonic modulatory role with regard to striatal dopamine (DA) transmission. The present study was designed to examine the effects of Ro15-1788, a benzodiazepine (BZ) receptor antagonist, and SR 95531, a GABAA receptor antagonist, on striatal extracellular DA (DA[e]) concentrations in anesthetized and awake rats using the technique of in vivo microdialysis. Local administration of Ro15-1788 resulted in a dose-dependent increase in DA[e] in both anesthetized and awake animals. The Ro15-1788-induced increase in DA[e] was blocked by coadministration of the BZ agonist diazepam, as well as GABA. Local administration of SR 95531 also resulted in a dose-dependent alteration in striatal DA levels in both anesthetized and awake animals. The SR 95531-induced increase in DA was blocked by coadministration of GABA. The results suggest that GABA may play a tonic inhibitory role with regard to striatal DA transmission.
Gruen
R J
RJ
Department of Psychiatry, New York University, NY 10003.
Friedhoff
A J
AJ
Coale
A
A
Moghaddam
B
B
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis / Q000379:methods; D003975:Diazepam / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D005442:Flumazenil / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D008297:Male; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*
D058787:GABA-A Receptor Antagonists; D011724:Pyridazines; D005442:Flumazenil; C049853:gabazine; D003975:Diazepam; D004298:Dopamine