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 mu l/min. Administr ation of the nonselective agonist pilocarpine at 10 mM increased stria tal dopamine release and decreased extracellular GABA and glutamate ov erflow. Perfusion with the muscarinic M-2 antagonist methoctramine at 75 mu M increased extracellular dopamine and glutamate concentrations but exerted no changes on extracellular GABA levels. Intrastriatal adm inistration of the M-1 antagonist pirenzepine at 0.05 mu M decreased e xtracellular dopamine overflow. Application of pirenzepine (0.05 and 5 mu M) exerted no effects on the measured GABA or glutamate levels. Th ere are thus important differences in applied doses of muscarinic drug s needed to obtain modulatory effects. High doses of agonists are prob ably needed to superimpose on the background of tonic influences of st riatal acetylcholine, whereas antagonists can block the receptors in s mall doses. We further suggest that M-1 receptors might tonically faci litate striatal dopamine release, that M-2 receptors might tonically i nhibit striatal glutamate efflux, and that acetylcholine does not exer t tonic effects on striatal GABA release, The link with the pilocarpin e animal model for temporal lobe epilepsy will be discussed.