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Endocannabinoid modulation of hyperaemia evoked by physiologically relevant stimuli in the rat primary somatosensory cortex. Br J Pharmacol 2010 Jun;160(3):736-46

Date

07/02/2010

Pubmed ID

20590576

Pubmed Central ID

PMC2931572

DOI

10.1111/j.1476-5381.2010.00772.x

Scopus ID

2-s2.0-77952633980   8 Citations

Abstract

BACKGROUND AND PURPOSE: 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.

EXPERIMENTAL APPROACH: 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.

KEY 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 AND IMPLICATIONS: 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.

Author List

Ho WS, Patel S, Thompson JR, Roberts CJ, Stuhr KL, Hillard CJ

Authors

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Christopher J. Roberts MD, PhD Assistant Professor in the Anesthesiology department at Medical College of Wisconsin
Jonathan R. Thompson MD Assistant Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Arachidonic Acids
Benzoxazines
Bicuculline
Cannabinoid Receptor Modulators
Endocannabinoids
Functional Laterality
Glycerides
Hyperemia
Male
Morpholines
Naphthalenes
Piperidines
Proto-Oncogene Proteins c-fos
Pyrazoles
Rats
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB1
Somatosensory Cortex
Vibrissae
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0