title: Presynaptic TRPV1 vanilloid receptor function is age- but not CB1 cannabinoid receptor-dependent in the rodent forebrain.
abstract: Neocortical and striatal TRPV1 (vanilloid or capsaicin) receptors (TRPV1Rs) are excitatory ligand-gated ion channels, and are implicated in psychiatric disorders. However, the purported presynaptic neuromodulator role of TRPV1Rs in glutamatergic, serotonergic or dopaminergic terminals of the rodent forebrain remains little understood. With the help of patch-clamp electrophysiology and neurochemical approaches, we mapped the age-dependence of presynaptic TRPV1R function, and furthermore, we aimed at exploring whether the presence of CB1 cannabinoid receptors (CB1Rs) influences the function of the TRPV1Rs, as both receptor types share endogenous ligands. We found that the major factor which affects presynaptic TRPV1R function is age: by post-natal day 13, the amplitude of capsaicin-induced release of dopamine and glutamate is halved in the rat striatum, and two weeks later, capsaicin already loses its effect. However, TRPV1R receptor function is not enhanced by chemical or genetic ablation of the CB1Rs in dopaminergic, glutamatergic and serotonergic terminals of the mouse brain. Altogether, our data indicate a possible neurodevelopmental role for presynaptic TRPV1Rs in the rodent brain, but we found no cross-talk between TRPV1Rs and CB1Rs in the same nerve terminal.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Köles
authors.forename: Pedro
authors.initials: P
authors.lastname: Garção
authors.forename: Zoltán S
authors.initials: ZS
authors.lastname: Zádori
authors.forename: Samira G
authors.initials: SG
authors.lastname: Ferreira
authors.forename: Bárbara S
authors.initials: BS
authors.lastname: Pinheiro
authors.forename: Carla S
authors.initials: CS
authors.lastname: da Silva-Santos
authors.forename: Catherine
authors.initials: C
authors.lastname: Ledent
authors.forename: Attila
authors.initials: A
authors.lastname: Köfalvi
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000254:growth & development / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017729:Presynaptic Terminals / Q000378:metabolism / Q000502:physiology; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D050916:TRPV Cation Channels / Q000187:drug effects / Q000502:physiology*
chemical_list: D043884:Receptor, Cannabinoid, CB1; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D012701:Serotonin; D018698:Glutamic Acid; D002211:Capsaicin; D004298:Dopamine
keywords: 3Rs; 4-AP; 4-aminopyridine; 7-, 14-, 29- and 60-day-old; 7D, 14D, 29D, 60D; ACEA; ARC; ARRIVE; AUC; American Radiolabeled Chemicals; Animal Research: Reporting In Vivo Experiments; BCA; BSA; CB(1) cannabinoid receptor; CB(1)R; DMSO; DPM; DTT; Dopamine; ECF; EDTA; EGTA; FR%; Federation for Laboratory Animal Science Associations; Felasa; GABA; Glutamate; HEPES; KHR; KO; Krebs-HEPES-Ringer; LiGTP; MAO B; MgATP; N-(2-hydroxyethyl)piperazine-N′-(2-ethanesulfonic acid); N-arachidonyl dopamine; NADA; NO; PMSF; PVDF; RTX; SDS; SEM; Serotonin; Striatum; TBS-T; TRPV(1) vanilloid receptor; TRPV(1)R and TRPV(4)R; Tris; Tris-buffered saline with Tween 20; WT; aCSF; arachidonyl-2′-chloroethylamide; area-under-the-curve; artificial cerebrospinal fluid; bicinchoninic acid; bovine serum albumin; cannabinoid receptor type 1; dimethyl sulfoxide; disintegration per minute; dithiothreitol; enhanced chemi-fluorescence; ethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid; ethylenediaminetetraacetic acid; fractional release %; knockout; lithium guanozine triphosphate; magnesium adenosine triphosphate; monoamine oxidase B; nitric oxide; phenylmethanesulfonyl fluoride; polyvinylidene difluoride; replacement, reduction, refinement; resiniferatoxin; sEPSCs; sodium dodecyl sulfate; spontaneous excitatory postsynaptic currents; standard error of the mean; transient release potential receptor vanilloid type 4; tris(hydroxymethyl)aminomethane; wild-type; γ-aminobutyric acid