Muscarinic modulation of striatal dopamine, glutamate, and GABA release, as measured with in vivo microdialysis.
Intrastriatal microdialysis was used to administer muscarinic drugs in freely moving rats for 40 min at a flow rate of 2 microl/min. Administration of the nonselective agonist pilocarpine at 10 mM increased striatal dopamine release and decreased extracellular GABA and glutamate overflow. Perfusion with the muscarinic M2 antagonist methoctramine at 75 microM increased extracellular dopamine and glutamate concentrations but exerted no changes on extracellular GABA levels. Intrastriatal administration of the M1 antagonist pirenzepine at 0.05 microM decreased extracellular dopamine overflow. Application of pirenzepine (0.05 and 5 microM) exerted no effects on the measured GABA or glutamate levels. There are thus important differences in applied doses of muscarinic drugs needed to obtain modulatory effects. High doses of agonists are probably needed to superimpose on the background of tonic influences of striatal acetylcholine, whereas antagonists can block the receptors in small doses. We further suggest that M1 receptors might tonically facilitate striatal dopamine release, that M2 receptors might tonically inhibit striatal glutamate efflux, and that acetylcholine does not exert tonic effects on striatal GABA release. The link with the pilocarpine animal model for temporal lobe epilepsy will be discussed.
Smolders
I
I
Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Belgium.
Bogaert
L
L
Ebinger
G
G
Michotte
Y
Y
D000818:Animals; D018678:Cholinergic Agents / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D003959:Diamines / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018678:Cholinergic Agents; D003959:Diamines; D010276:Parasympatholytics; D010277:Parasympathomimetics; D010862:Pilocarpine; D010890:Pirenzepine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C054938:methoctramine; D004298:Dopamine