title: Endocannabinoid modulation of hyperaemia evoked by physiologically relevant stimuli in the rat primary somatosensory cortex.
abstract: OBJECTIVE
  In vitro studies demonstrate that cannabinoid CB(1) receptors subserve activity-dependent suppression of inhibition in the neocortex. To examine this mechanism in vivo, we assessed the effects of local changes in CB(1) receptor activity on somatosensory cortex neuronal activation by whisker movement in rats.
  
  
  METHODS
  Laser Doppler flowmetry and c-Fos immunohistochemistry were used to measure changes in local blood flow and neuronal activation, respectively. All drugs were applied directly to the cranium above the whisker barrel fields of the primary somatosensory cortex.
  
  
  RESULTS
  The CB(1) receptor agonist WIN55212-2 potentiated the hyperaemia induced by whisker movement and this potentiation was occluded by bicuculline. The CB(1) receptor antagonists, rimonabant and AM251, inhibited hyperaemic responses to whisker movement; indicating that activation of endogenous CB(1) receptors increased during whisker movement. Whisker movement-induced expression of c-Fos protein in neurons of the whisker barrel cortex was inhibited by rimonabant. Movement of the whiskers increased the 2-arachidonoylglycerol content in the contralateral, compared to the ipsilateral, sensory cortex.
  
  
  CONCLUSIONS
  These results support the hypothesis that endocannabinoid signalling is recruited during physiologically relevant activation of the sensory cortex. These data support the hypothesis that the primary effect of CB(1) receptor activation within the activated whisker barrel cortex is to inhibit GABA release, resulting in disinhibition of neuronal activation. These studies provide physiological data involving endocannabinoid signalling in activity-dependent regulation of neuronal activation and provide a mechanistic basis for the effects of cannabis use on sensory processing in humans.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: W-Sv
authors.initials: WS
authors.lastname: Ho
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.forename: J R
authors.initials: JR
authors.lastname: Thompson
authors.forename: C J
authors.initials: CJ
authors.lastname: Roberts
authors.forename: K L
authors.initials: KL
authors.lastname: Stuhr
authors.forename: C J
authors.initials: CJ
authors.lastname: Hillard
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D048588:Benzoxazines / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000502:physiology; D063388:Endocannabinoids; D007839:Functional Laterality; D005989:Glycerides / Q000378:metabolism; D006940:Hyperemia / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D000077285:Rimonabant; D013003:Somatosensory Cortex / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014738:Vibrissae / Q000502:physiology
chemical_list: D001095:Arachidonic Acids; D048588:Benzoxazines; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D016760:Proto-Oncogene Proteins c-fos; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C094503:glyceryl 2-arachidonate; D000077285:Rimonabant; D001640:Bicuculline