Nti-inflammatory Property of the Cannabinoid Agonist In-55212-2 in a Rodent Model of Chronic Brain Nflammation

bstract—Cannabinoid receptors (CBr) stimulation induces umerous central and peripheral effects. A growing interest n the beneficial properties of manipulating the endocannabioid system has led to the possible involvement of CBr in the ontrol of brain inflammation. In the present study we examned the effect of the CBr agonist, (R)-( )-[2,3-dihydro-5ethyl-3-(4-morpholinylmethyl)-pyrrolo[1,2,3-de]-1,4benzoazin-6-yl]-1-naphthalenyl-methanone mesylate (WIN-55212), on microglial activation and spatial memory performance, sing a well-characterized animal model of chronic brain nflammation produced by the infusion of lipopolysaccharide LPS, 250 ng/h for 3 weeks) into the fourth ventricle of young ats. WIN-55212-2 (0.5 or 1.0 mg/kg/day, i.p.) was adminisered for 3 weeks. During the third week of treatment, spatial emory ability was examined using the Morris water-maze ask. We found that 0.5 and 1 mg/kg WIN-55212-2 reduced the umber of LPS-activated microglia, while 1 mg/kg WIN5212-2 potentiated the LPS-induced impairment of perforance in the water maze task. Cannabinoid receptors 1 were ot expressed by microglia and astrocytes, suggesting an ndirect effect of WIN-55212-2 on microglia activation and emory impairment. Our results emphasize the potential use f CBr agonists in the regulation of inflammatory processes ithin the brain; this knowledge may lead to the use of CBr gonists in the treatment of neurodegenerative diseases asociated with chronic neuroinflammation, such as Alzheimer isease. © 2006 IBRO. Published by Elsevier Ltd. All rights eserved.