title: Activation of CB1 cannabinoid receptors in the dorsolateral periaqueductal gray reduces the expression of contextual fear conditioning in rats.
abstract: BACKGROUND
  Conditioned fear to context causes freezing and cardiovascular changes in rodents and has been used to measure anxiety. It also activates the dorsolateral column of the periaqueductal gray (dlPAG). Microinjections of cannabinoid agonists into the dlPAG produced anxiolytic-like effects in the elevated plus maze, but the effects of these treatments on fear conditioning remains unknown.
  
  
  OBJECTIVE
  The objective of this study was to verify if intra-dlPAG injection of the CB1 cannabinoid receptor agonist anandamide (AEA) or the anandamide transport inhibitor AM404 would attenuate behavioral (freezing) and cardiovascular (increase of arterial pressure and heart rate) responses of rats submitted to a contextual fear-conditioning paradigm.
  
  
  METHODS
  Male Wistar rats with cannulae aimed at the dlPAG were re-exposed to a chamber where they had received footshocks 48 h before. Fifteen minutes before the test, the animals received a first intra-dlPAG injection of vehicle or AM251, a CB1 receptor antagonist (100 pmol/200 nl), followed 5 min later by vehicle, AEA (5 pmol/200 nl) or AM404 (50 pmol/200 nl). Freezing and cardiovascular responses were recorded for 10 min.
  
  
  RESULTS
  Freezing and cardiovascular responses were reduced by administration of either AEA or AM404 into the dlPAG before re-exposition to the aversively conditioned context. These effects were abolished when the animals were locally pretreated with AM251. The latter drug, even at a higher dose (300 pmol), was ineffective when administered alone into the dlPAG.
  
  
  CONCLUSIONS
  The results suggest that facilitation of endocannabinoid-mediated neurotransmission in the dlPAG, through activation of local CB1 receptors, attenuates the expression of contextual fear responses.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of Sao Paulo, Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, São Paulo, Brazil. leoresstel@yahoo.com.br
authors.forename: L B M
authors.initials: LB
authors.lastname: Resstel
authors.forename: S F
authors.initials: SF
authors.lastname: Lisboa
authors.forename: D C
authors.initials: DC
authors.lastname: Aguiar
authors.forename: F M A
authors.initials: FM
authors.lastname: Corrêa
authors.forename: F S
authors.initials: FS
authors.lastname: Guimarães
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D063388:Endocannabinoids; D005239:Fear / Q000523:psychology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008845:Microinjections; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D010487:Periaqueductal Gray / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000378:metabolism / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000037:antagonists & inhibitors
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D014179:Neurotransmitter Uptake Inhibitors; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251; C078814:anandamide; C107594:N-(4-hydroxyphenyl)arachidonylamide