GABAergic modulation of striatal cholinergic interneurons: an in vivo microdialysis study.
Striatal cholinergic interneurons have been shown to receive input from striatal gamma-aminobutyric acid (GABA)-containing cell elements. GABA is known to act on two different types of receptors, the GABAA and the GABAB receptor. Using in vivo microdialysis, we have studied the effect of intrastriatal application of the GABAA-selective compounds muscimol and bicuculline and the GABAB-selective compounds baclofen and 2-hydroxysaclofen, agonists and antagonists, respectively, at GABA receptors, on the output of striatal acetylcholine (ACh). Intrastriatal infusion of 1 and 10 mumol/L concentrations of the GABAA antagonist bicuculline resulted in a significant increase in striatal ACh output, whereas infusion of 1 and 10 mumol/L concentrations of the GABAA agonist muscimol significantly decreased the output of striatal ACh. Both compounds were ineffective in changing the output of striatal ACh at lower concentrations. Infusion of concentrations up to 100 mumol/L of the GABAB-selective antagonist 2-hydroxy-saclofen failed to affect striatal ACh output, whereas infusion of 10 and 100 mumol/L baclofen, but not 0.1 and 1 mumol/L baclofen, significantly decreased the output of striatal ACh. Thus, agonist-stimulation of GABAA and GABAB receptors decreases the output of striatal ACh in a dose-dependent fashion, whereas the GABAAergic system appears to inhibit tonically the output of striatal ACh via GABAA receptors, but not via GABAB receptors. We hypothesize that although GABAA mediated regulation of striatal ACh occurs via GABA receptors on the cholinergic neuron, the GABAB mediated effects may be explained by presynaptic inhibition of the glutamatergic input of the striatal cholinergic neuron.
DeBoer
P
P
Center for Molecular and Behavioral Neuroscience, Aidekman Research Center, Rutgers University, Newark, New Jersey.
Westerink
B H
BH
D000109:Acetylcholine / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D017551:Microdialysis / Q000379:methods; D009118:Muscimol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D000109:Acetylcholine; D001640:Bicuculline