title: Effects of glutamate NMDA and TRPV1 receptor antagonists on the biphasic responses to anandamide injected into the dorsolateral periaqueductal grey of Wistar rats.
abstract: BACKGROUND
  The endocannabinoid and endovanniloid anandamide (AEA) exerts biphasic effects when injected into the dorsolateral periaqueductal grey (dlPAG) in rats submitted to threatening situations. Whereas lower doses of AEA induce anxiolytic-like effects by activating cannabinoid CB1 receptors, no effects are observed with higher doses, possibly due to the simultaneous activation of transient receptor potential vanilloid type 1 (TRPV1) receptors. This activation would facilitate glutamatergic neurotransmission.
  
  
  OBJECTIVE
  Considering that the blockade of TRPV1 or NMDA receptors in the dlPAG induces anxiolytic-like effects, we tested the hypothesis that facilitation of glutamate transmission through TRPV1 is responsible for the lack of anxiolytic-like effect observed with high AEA doses.
  
  
  METHODS
  Male Wistar rats with a unilateral cannula aimed at the dlPAG received injections of an ineffective dose of AP7 (an NMDA antagonist, 1 nmol) or capsazepine (CPZ, a TRPV1 antagonist, 10 nmol), followed by a high dose of AEA (50 and 200 pmol) and were exposed to the elevated plus maze (EPM) or the Vogel conflict test (VCT).
  
  
  RESULTS
  AP7, CPZ, or AEA did not induce any significant effects when administered alone. However, AP7 or CPZ prior to AEA significantly increased the percentage of entries and time spent in the open arms of EPM and the number of punished licks in the VCT suggesting an anxiolytic-like effect.
  
  
  CONCLUSIONS
  These results suggest that the lack of anxiolytic-like effect of higher AEA doses is due to facilitation of glutamate release in the dlPAG, probably via activation of TRPV1 receptors in this structure.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, São Paulo 14049900, Brazil.
authors.forename: Manoela V
authors.initials: MV
authors.lastname: Fogaça
authors.forename: Felipe V
authors.initials: FV
authors.lastname: Gomes
authors.forename: Fabrício A
authors.initials: FA
authors.lastname: Moreira
authors.forename: Francisco S
authors.initials: FS
authors.lastname: Guimarães
authors.forename: Daniele C
authors.initials: DC
authors.lastname: Aguiar
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D010487:Periaqueductal Gray / Q000187:drug effects; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*
chemical_list: D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D016194:Receptors, N-Methyl-D-Aspartate; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D015763:2-Amino-5-phosphonovalerate; C071423:capsazepine; C031231:2-amino-7-phosphonoheptanoic acid; D002211:Capsaicin; C078814:anandamide