title: The endocannabinoid, endovanilloid and nitrergic systems could interact in the rat dorsolateral periaqueductal gray matter to control anxiety-like behaviors.
abstract: Cannabinoid compounds usually produce biphasic effects in the modulation of emotional responses. Low doses of the endocannabinoid anandamide (AEA) injected into the dorsolateral periaqueductal gray matter (dlPAG) induce anxiolytic-like effects via CB1 receptors activation. However, at higher doses the drug loses this effect, in part by activating Transient Receptor Potential Vanilloid Type 1 (TRPV1). Activation of these latter receptors could induce the formation of nitric oxide (NO). Thus, the present study tested the hypothesis that at high doses AEA loses it anxiolytic-like effect by facilitating, probably via TRPV1 receptor activation, the formation of NO. Male Wistar rats received combined injections into the dlPAG of vehicle, the TRPV1 receptor antagonist 6-iodo-nordihydrocapsaicin or the NO scavenger carboxy-PTIO (c-PTIO), followed by vehicle or AEA, and were submitted to the elevated plus maze (EPM) or the Vogel conflict test (VCT). A low dose (5pmol) of AEA produced an anxiolytic-like effect that disappeared at higher doses (50 and 200pmol). The anxiolytic-like effects of these latter doses, however, were restored after pre-treatment with a low and ineffective dose of c-PTIO in both animal models. In addition, the combined administration of ineffective doses of 6-iodo-nordihydrocapsaicin (1nmol) and c-PTIO (0.3nmol) produced an anxiolytic-like response. Therefore, these results support the hypothesis that intra-dlPAG injections of high doses of AEA lose their anxiolytic effects by favoring TRPV1 receptors activity and consequent NO formation, which in turn could facilitate defensive responses.
authors.affiliation: Department of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo (FMRP-USP), Bandeirantes Avenue, 3900, Ribeirão Preto, 14049-900 São Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo (USP), Brazil.
authors.forename: Priscila A
authors.initials: PA
authors.lastname: Batista
authors.affiliation: Department of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo (FMRP-USP), Bandeirantes Avenue, 3900, Ribeirão Preto, 14049-900 São Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo (USP), Brazil. Electronic address: manoelafogaca@usp.br.
authors.forename: Manoela V
authors.initials: MV
authors.lastname: Fogaça
authors.affiliation: Department of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo (FMRP-USP), Bandeirantes Avenue, 3900, Ribeirão Preto, 14049-900 São Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo (USP), Brazil.
authors.forename: Francisco S
authors.initials: FS
authors.lastname: Guimarães
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000473:pathology*; D001095:Arachidonic Acids / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004195:Disease Models, Animal; D004326:Drinking / Q000187:drug effects; D004347:Drug Interactions; D063388:Endocannabinoids / Q000378:metabolism* / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008845:Microinjections; D009569:Nitric Oxide / Q000378:metabolism*; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000378:metabolism*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D003497:Cyclic N-Oxides; D063388:Endocannabinoids; D016166:Free Radical Scavengers; D007093:Imidazoles; D053284:Polyunsaturated Alkamides; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; D009569:Nitric Oxide; C517386:nordihydrocapsaicin; D002211:Capsaicin; C078814:anandamide
keywords: Anandamide; Anxiety; Endocannabinoid; Endovanilloid; Nitric oxide; Periaqueductal gray matter; TRPV(1) receptor