BRAIN CB1 RECEPTOR EXPRESSION FOLLOWING LIPOPOLYSACCHARIDE-INDUCED INFLAMMATION

Cannabinoid 1 receptors (CB1) are highly expressed on presynaptic terminals in the brain where they are importantly involved in the control of neurotransmitter release. Alteration of CB1 expression is associated with a variety of neurological and psychiatric disorders. There is now compelling evidence that peripheral inflammatory disorders are associated with depression and cognitive impairments. These can be modeled in rodents with peripheral administration of lipopolysaccharide (LPS), but central effects of this treatment remain to be fully elucidated. As a reduction in endocannabinoid tone is thought to contribute to depression, we asked whether the expression of CB1 in the CNS is altered following LPS treatment. CD1 mice received LPS (0.1-1 mg/kg, ip) and 6 h later activated microglial cells were observed only in circumventricular organs and only at the higher dose. At 24 h, activated microglial cells were identified in other brain regions, including the hippocampus, a structure implicated in some mood disorders. Immunohistochemistry and real-time polymerase chain reaction (PCR) were utilized to evaluate the change of CB1 expression 24 h after inflammation. LPS induced an increase of CB1 mRNA in the hippocampus and brainstem. Subsequent immunohistochemical analysis revealed reduced CB1 in the hippocampus, especially in CA3 pyramidal layer. Analysis of co-localization with markers of excitatory and inhibitory terminals indicated that the decrease in CB1 expression was restricted to glutamatergic terminals. Despite widespread microglial activation, these results suggest that peripheral LPS treatment leads to limited changes in CB1 expression in the brain. (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.