Endocannabinoid modulation of hyperaemia evoked by physiologically relevant stimuli in the rat primary somatosensory cortex

• Published in: British journal of pharmacology 2010-06, Vol.160 (3), p.736-746
• Main Authors: Ho, W‐SV, Patel, S, Thompson, JR, Roberts, CJ, Stuhr, KL, Hillard, CJ
• Format: Article
• Language: English
• Subjects: 2-Arachidonylglycerol; 2‐arachidonoylglycerol; Anandamide; Animals; Antagonists; Arachidonic Acids - metabolism; Benzoxazines - pharmacology; Bicuculline; Bicuculline - pharmacology; Brain; c-Fos protein; Cannabinoid CB1 receptors; Cannabinoid Receptor Modulators - physiology; Cannabis; CB1 cannabinoid receptor; Cortex; Cortex (barrel); Cortex (somatosensory); Data processing; Doppler effect; Drug abuse; endocannabinoid; Endocannabinoids; Functional Laterality; gamma -Aminobutyric acid; Glycerides - metabolism; hyperaemic response; Hyperemia - metabolism; Hyperemia - physiopathology; Immunohistochemistry; Information processing; laser Doppler flowmetry; Lasers; Male; Morpholines - pharmacology; Naphthalenes - pharmacology; Piperidines - pharmacology; Potentiation; Proto-Oncogene Proteins c-fos - metabolism; Pyrazoles - pharmacology; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1 - agonists; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Receptor, Cannabinoid, CB1 - physiology; Research Papers; Rimonabant; Rodents; Sensory integration; Somatosensory Cortex - blood supply; Somatosensory Cortex - drug effects; Somatosensory Cortex - metabolism; Somatosensory Cortex - physiology; Vibrissae - physiology; whisker barrel cortex
• ISSN: 0007-1188; 1476-5381; 1476-5381
• DOI: 10.1111/j.1476-5381.2010.00772.x

Background and purpose:  In vitro studies demonstrate that cannabinoid CB1 receptors subserve activity‐dependent suppression of inhibition in the neocortex. To examine this mechanism in vivo, we assessed the effects of local changes in CB1 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 CB1 receptor agonist WIN55212‐2 potentiated the hyperaemia induced by whisker movement and this potentiation was occluded by bicuculline. The CB1 receptor antagonists, rimonabant and AM251, inhibited hyperaemic responses to whisker movement; indicating that activation of endogenous CB1 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 CB1 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. This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00831.x