Activation of muscarinic M3-like receptors and β-adrenoceptors, but not M2-like muscarinic receptors or α-adrenoceptors, directly modulates corticostriatal neurotransmission in vitro

• Published in: Neuroscience Vol. 90; no. 1; pp. 95 - 105
• Main Authors: Niittykoski, M, Ruotsalainen, S, Haapalinna, A, Larson, J, Sirviö, J
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.01.1999; Elsevier
• Subjects: (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride - pharmacology; 6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology; Adrenergic alpha-Agonists - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Adrenergic beta-Agonists - pharmacology; Adrenergic Fibers - drug effects; Adrenergic Fibers - physiology; adrenoceptors; Animals; aniracetam; Biological and medical sciences; Carbachol - pharmacology; Central nervous system; Cerebral Cortex - drug effects; Cerebral Cortex - physiology; Cholinergic Fibers - drug effects; Cholinergic Fibers - physiology; cholinergic receptors; Corpus Striatum - drug effects; Corpus Striatum - physiology; Diamines - pharmacology; Electrophysiology; Excitatory Amino Acid Agonists - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Fundamental and applied biological sciences. Psychology; glutamate; Glutamic Acid - metabolism; Imidazoles - pharmacology; Isoproterenol - pharmacology; Male; Medetomidine; Mice; Mice, Inbred DBA; Muscarinic Agonists - pharmacology; Muscarinic Antagonists - pharmacology; neurotransmission; Phenylephrine - pharmacology; Piperidines - pharmacology; Pirenzepine - pharmacology; Pyrrolidinones - pharmacology; Receptor, Muscarinic M2; Receptor, Muscarinic M3; Receptors, Adrenergic, alpha - drug effects; Receptors, Adrenergic, alpha - physiology; Receptors, Adrenergic, beta - drug effects; Receptors, Adrenergic, beta - physiology; Receptors, AMPA - drug effects; Receptors, AMPA - physiology; Receptors, Muscarinic - drug effects; Receptors, Muscarinic - physiology; Scopolamine - pharmacology; striatum; Synaptic Transmission - drug effects; Vertebrates: nervous system and sense organs; McN-A-343, 4-[[[(3-chlorophenyl)amino]carbonyl]oxy]- N, N, N-trimethyl-2-butyn-1-aminium chloride; cholinergic receptors; neurotransmission; EPSP, excitatory postsynaptic potential; GluR, glutamate receptor; striatum; aniracetam; aCSF, artificial cerebrospinal fluid; CNQX, 6-cyano-7-nitroquinoxaline-2,3-dione; adrenoceptors; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; glutamate; 4-DAMP, 4-diphenylacetoxy- N-methyl-piperidine; M3 Muscarinic receptor; Rodentia; Central nervous system; Corpus striatum; Glutamate; β-Adrenergic receptor; Vertebrata; Mammalia; Mouse; α-Adrenergic receptor; Synaptic transmission; Excitatory aminoacid; Neurotransmitter; M2 Muscarinic receptor; Brain (vertebrata)
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(98)00447-3

The aim of this study was to characterize the modulation of synaptic transmission in the glutamatergic corticostriatal pathway by cholinergic and adrenergic receptors. In coronal slices of mouse brain, negative-going field potentials were recorded in the dorsal striatum in response to stimulation of the overlying white matter, and their susceptibility to various pharmacological manipulations was studied. The responses were mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors, since they were augmented by aniracetam (0.5–1.5 mM), a positive modulator of AMPA-type glutamate receptors, and blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (≥10 μM), a selective antagonist of AMPA receptors. Carbachol (10 μM), a muscarinic agonist, reduced the size of responses and abolished paired-pulse depression; these effects being consistent with previous studies indicating that muscarinic activation inhibits release of glutamate in the corticostriatal pathway. Muscarinic antagonists could block the effect of carbachol. Their rank order was: 10 μM scopolamine (a non-selective muscarinic antagonist)≥1 μM 4-diphenylacetoxy- N-methyl-piperidine (M3/M1 antagonist)>1 μM pirenzepine (M1 antagonist)>10 μM methoctramine (M2 antagonist). McN-A-343 (1–10 μM), an M1 muscarinic agonist, was ineffective in this preparation. In contrast, isoproterenol (10–30 μM), a β-adrenergic agonist, slightly increased the synaptic responses, but it did not affect paired-pulse depression. None of α-adrenergic agents (30 nM–1.0 μM dexmedetomidine, an α 2-adrenergic agonist, 0.3 μM atipamezole, an α 2-adrenergic antagonist or 30 μM phenylephrine, an α 1-adrenergic agonist) influenced the size of the responses; neither did these drugs alter paired-pulse depression. These results indicate that the activation of striatal M3-like muscarinic receptors and β-adrenoceptors, but not M2-like muscarinic receptors and α-adrenoceptors, modulates directly corticostriatal glutamatergic neurotransmission.