title: Anxiogenic-like effect induced by TRPV1 receptor activation within the dorsal periaqueductal gray matter in mice.
abstract: Pharmacological manipulation of TRPV1 (Transient Receptor Potential Vanilloid type-1) receptors has been emerging as a novel target in the investigation of anxiety states. Here, we attempt to show the role played by the TRPV1 receptors within the dorsal periaqueductal gray matter (dPAG), a midbrain structure strongly involved in the modulation of anxiety. Anxiety was assessed by recording spatiotemporal [percent open arm entries (%OE) and percent open arm time (%OT)] and ethological [e.g., head dipping (HD), stretched-attend postures (SAP)] measures in mice exposed to the elevated plus-maze (EPM). Mice received an intra-dPAG injection of the TRPV1 agonist capsaicin (0, 0.01, 0.1 or 1.0nmol/0.2μL; Experiment 1) or antagonist capsazepine (0, 10, 30 or 60nmol/0.2μL; Experiment 2), or combined injections of capsazepine (30nmol) and capsaicin (1.0nmol) (Experiment 3), and were exposed to the EPM to record spatiotemporal and ethological measures. While capsaicin produced an anxiogenic-like effect (it reduced %OE and %OT and frequency of SAP and HD in the open arms), capsazepine did not change any behavior in the EPM. However, when injected before capsaicin (1.0nmol), intra-dPAG capsazepine (30nmol-a dose devoid of intrinsic effects) antagonized completely the anxiogenic-like effect of the TRPV1 agonist. These results suggest that the anxiogenic-like effect produced by capsaicin is primarily due to TRPV1 activation within the dPAG in mice, but that dPAG TRPV1 receptors do not exert a tonic control over defensive behavior in mice exposed to the EPM.
authors.affiliation: Joint Graduate Program in Physiological Sciences, UFSCar/UNESP, São Carlos, SP, 13565-905, Brazil.
authors.forename: Diego Cardozo
authors.initials: DC
authors.lastname: Mascarenhas
authors.forename: Karina Santos
authors.initials: KS
authors.lastname: Gomes
authors.forename: Ricardo Luiz
authors.initials: RL
authors.lastname: Nunes-de-Souza
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008845:Microinjections; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D014151:Anti-Anxiety Agents; D004338:Drug Combinations; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C071423:capsazepine; D002211:Capsaicin