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  • Title: Mutual inhibitory effects between dopamine and carbachol on the excitatory synaptic transmission in the rat neostriatum.
    Author: Hsu KS, Huang CC, Gean PW.
    Journal: J Neurosci Res; 1996 Oct 01; 46(1):34-41. PubMed ID: 8892103.
    Abstract:
    The interactions between dopamine and carbachol on the excitatory synaptic transmission were studied in rat neostriatal slices using an intracellular recording method. Excitatory postsynaptic potentials (EPSPs) were evoked by cortical stimulation. Application of dopamine (DA; 0.1 microM) or carbachol (0.1 microM) produced a dramatic and reversible inhibition of the EPSP amplitude. The inhibitory effect induced by carbachol was markedly attenuated in the presence of either DA (0.1 microM) or the selective D2 dopaminergic receptor agonist (+/-)-2-(N-phenylethyl-N-propyl) amino-5-hydroxytertralin (PPHT; 0.1 microM), but not by the D1 dopaminergic receptor agonist (+/-)-7, 8-dihydroxy-3-allyl-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine (SKF-38393; 0.1 microM) or the D3 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 microM). Conversely, muscarinic receptor activation with carbachol (0.1 microM) also completely abolished the DA-induced depression of the EPSP amplitude. In addition, the inhibitory effect of DA on the carbachol-induced depression of the EPSP amplitude was antagonized by sulpiride (1 microM), a selective D2 dopaminergic receptor antagonist. However, D1 dopaminergic receptor antagonist (+/-)-7-bromo-8-hydroxy-3-methyl-1-phenyl-2, 3, 4, 5-tetrahydro-3-benzazepine (SKF-83566; 1 microM) did not affect DA's inhibition. Rp-adenosine-3',5'-cyclic monophosphothioate (Rp-cAMPS; 25 microM), a potent inhibitor of cAMP-dependent protein kinase A (PKA), alone decreased the amplitude of EPSP below baseline values and mimicked the inhibitory effect of DA on the carbachol-induced depression of the EPSP amplitude. Based on these findings, we conclude that the inhibitory effects of D2 dopaminergic receptor and muscarinic receptor activation on the excitatory synaptic transmission in the neostriatum are non-additive and therefore are antagonistic interactions. furthermore, the effect of muscarinic receptor stimulation will depend on the extent of D2 dopaminergic receptor activation and the modulation of the cellular PKA-dependent messenger system seems to contribute to their interactions.
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