MUTUAL INHIBITORY EFFECTS BETWEEN DOPAMINE AND CARBACHOL ON THE EXCITATORY SYNAPTIC TRANSMISSION IN THE RAT NEOSTRIATUM

The interactions between dopamine and carbachol on the excitatory syna ptic transmission were studied in rat neostriatal slices using an intr acellular recording method. Excitatory postsynaptic potentials (EPSPs) were evoked by cortical stimulation. Application of dopamine (DA; 0.1 mu M) or carbachol (0.1 mu M) produced a dramatic and reversible inhi bition of the EPSP amplitude. The inhibitory effect induced by carbach ol was markedly attenuated in the presence of either DA (0.1 mu M) or the selective D-2 dopaminergic receptor agonist (+/-)-2-(N-phenylethyl -N-propyl) amino-5-hydroxytertralin (PPHT; 0.1 mu M), but not by the D -2 dopaminergic receptor agonist (+/-)-7,8-dihydroxy-3-allyl-1-phenyl- 2,3,4, 5-tetrahydro-1H-3-benzazepine (SKF-38393; 0.1 mu M) or the D-1 dopaminergic receptor agonist R(-)-(4aS,10bS)-3,4,4a, 10b-tetrahydro-4 -propyl-2H,5H-[1] benzogyrano-[4,3-b]-1, 4-oxazin-9-ol (PD-128,907; 0. 1 mu M). Conversely, muscarinic receptor activation with carbachol (0. 1 mu M) also completely abolished the DA-induced depression of the EPS P amplitude. In addition, the inhibitory effect of DA on the carbachol -induced depression of the EPSP amplitude was antagonized by sulpiride (1 mu M), a selective D-2 dopaminergic receptor antagonist. However, D-1 dopaminergic receptor antagonist (+/-)-7-bromo-8-hydroxy-3-methyl- 1-phenyl-2,3,4, 5-tetrahydro-3-benzazepine (SKF-83566; 1 mu M) did not affect DA's inhibition. Rp-adenosine3',5'-cyclic monophosphothioate ( Rp-cAMPS; 25 mu M), a potent inhibitor of cAMP-dependent protein kinas e A (PKA), alone decreased the amplitude of EPSP below baseline values and mimicked the inhibitory effect of DA on the carbachol-induced dep ression of the EPSP amplitude. Based on these findings, we conclude th at the inhibitory effects of D-2 dopaminergic receptor and muscarinic receptor activation on the excitatory synaptic transmission in the neo striatum are non-additive and therefore are antagonistic interactions. Furthermore, the effect of muscarinic receptor stimulation will depen d on the extent of D-2 dopaminergic receptor activation and the modula tion of the cellular PKA-dependent messenger system seems to contribut e to their interactions. (C) 1996 Wiley-Liss, Inc.