MUSCARINIC DEPRESSION OF EXCITATORY SYNAPTIC TRANSMISSION MEDIATED BYTHE PRESYNAPTIC M3 RECEPTORS IN THE RAT NEOSTRIATUM

The effect of carbachol on the excitatory synaptic transmission was st udied in rat neostriatal neurons using intracellular and whole-cell vo ltage clamp-recording methods. Depolarizing excitatory postsynaptic po tentials (EPSPs) were evoked by cortical stimulation. Superfusion of c arbachol (0.01-3 mu M) reversibly decreases the EPSP amplitude in a co ncentration-dependent manner and with an estimated IC50 of 0.3 mu M. W hile, neither the N-methyl-D-aspartate (NMDA, 100 mu M)- nor (+/-)-alp ha-amino-3-hydroxy-5-methylisoxazole 4-propionic acid (AMPA, 100 mu M) -induced response was affected by carbachol (0.1 mu M). In addition, t he inhibitory effect induced by carbachol at a low concentration of 0. 1 mu M was attenuated by 4-diphenylacetoxy-N,N-methyl-piperidine (4-DA MP), a selective M3 muscarinic receptor antagonist. However, other mus carinic subtype (M1 or M2) antagonists could also block the inhibitory effect by carbachol 0.1 mu M. The rank order of antagonist potency wa s: 4-DAMP (M3 antagonist) > methoctramine (M2 antagonist) > pirenzepin e (M2 antagonist). Based on these findings, we conclude that carbachol at a low concentration (less than or equal to 0.1 mu M) reduced the e xcitatory response of neostriatal neurons following cortical stimulati on via presynaptic M3 muscarinic receptors located on the terminals of corticostriatal neurons.