Transient receptor potential vanilloid 1 channels control acetylcholine/2-arachidonoylglicerol coupling in the striatum

• Published in: Neuroscience Vol. 167; no. 3; pp. 864 - 871
• Main Authors: Musella, A, De Chiara, V, Rossi, S, Cavasinni, F, Castelli, M, Cantarella, C, Mataluni, G, Bernardi, G, Centonze, D
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 19-05-2010
• Subjects: Acetylcholine - metabolism; Amidohydrolases - antagonists & inhibitors; Amidohydrolases - metabolism; Animals; Arachidonic Acids - metabolism; Benzamides - pharmacology; Biological and medical sciences; Cannabinoid Receptor Modulators - metabolism; Capsaicin - pharmacology; Carbamates - pharmacology; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Endocannabinoids; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; gamma-Aminobutyric Acid - metabolism; Glycerides - metabolism; Inhibitory Postsynaptic Potentials - drug effects; Inhibitory Postsynaptic Potentials - physiology; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscarinic Agonists - pharmacology; Neural Inhibition - drug effects; Neural Inhibition - physiology; Neurology; Neuropharmacology; Organ Culture Techniques; Pharmacology. Drug treatments; Polyunsaturated Alkamides - metabolism; Psychodysleptics: hallucinogen; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Receptor, Metabotropic Glutamate 5; Receptor, Muscarinic M1 - agonists; Receptor, Muscarinic M1 - metabolism; Receptors, Metabotropic Glutamate - agonists; Receptors, Metabotropic Glutamate - metabolism; Sensory System Agents - pharmacology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; TRPV Cation Channels - drug effects; TRPV Cation Channels - metabolism; Vertebrates: nervous system and sense organs; FAAH; LTP; spontaneous excitatory postsynaptic currents; 2-arachidonoylglicerol; fatty acid amide hydrolase; IPSC; metabotropic glutamate receptor 5; CB1 receptors; 2AG; anandamide; AEA; diacylglycerol lipase; inhibitory postsynaptic current; mIPSCs; long-term depression; Ach; transient receptor potential vanilloid 1; sEPSCs; TRPV1; spontaneous IPSCs; sIPSCs; muscarinic receptors; endocannabinoids; acetylcholine; vanilloid receptors; DAGL; LTD; mGluR5; miniature IPSCs; long-term potentiation; CB1 cannabinoid receptor; Inhibitory postsynaptic current; Central nervous system; Electrophysiology; Basal ganglion; Corpus striatum; Cannabinoid; Encephalon; Anandamide; Cholinergic receptor; TRP ion channel; Endocannabinoid; Neurotransmitter; Acetylcholine; Muscarinic receptor; Vanilloid receptor
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.02.058

Abstract The neurotransmitter acetylcholine (Ach) controls both excitatory and inhibitory synaptic transmission in the striatum. Here, we investigated the involvement of the endocannabinoid system in Ach-mediated inhibition of striatal GABA transmission, and the potential role of transient receptor potential vanilloid 1 (TRPV1) channels in the control of Ach-endocannabinoid coupling. We found that inhibition of Ach degradation and direct pharmacological stimulation of muscarinic M1 receptors reduced striatal inhibitory postsynaptic currents (IPSCs) through the stimulation of 2-arachidonoylglicerol (2AG) synthesis and the activation of cannabinoid CB1 receptors. The effects of M1 receptor activation on IPSCs were occlusive with those of metabotropic glutamate receptor 5 stimulation, and were prevented in the presence of capsaicin, agonist of TRPV1 channels. Elevation of anandamide (AEA) tone with URB597, a blocker of fatty acid amide hydrolase, mimicked the effects of capsaicin, indicating that endogenous AEA acts as an endovanilloid substance in the control of M1-dependent 2AG-mediated synaptic effects in the striatum. Accordingly, both capsaicin and URB597 effects were absent in mice lacking TRPV1 channels. Pharmacological interventions targeting AEA metabolism and TRPV1 channels might be considered alternative therapeutic routes in disorders of striatal cholinergic or endocannabinoid neurotransmission.