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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Theiler's virus infection of the central nervous system (CNS) induces an immune-mediated demyelinating disease in susceptible mouse strains and serves as a relevant infection model for human multiple sclerosis (MS). Cannabinoids have been shown to exert beneficial effects on animal models of MS and evidence suggests that the endocannabinoid system plays a role in the tonic control of spasticity. In this study we show that OMDM1 [(R)-N-oleoyl-(1′-hydroxybenzyl)-2′-ethanolamine] and OMDM2 [(S)-N-oleoyl-(1′-hydroxybenzyl)-2′-ethanolamine], two selective inhibitors of the putative endocannabinoid transporter and hence of endocannabinoid inactivation, provide an effective therapy for Theiler murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Treatment of TMEV-infected mice with OMDM1 and OMDM2 enhanced anandamide levels in the spinal cord and ameliorated motor symptoms. This was associated with a down-regulation of inflammatory responses in the spinal cord. In addition we show that OMDM1 and OMDM2 down-regulate macrophage function by (i) decreasing the surface expression of major histocompatibility complex (MHC) class II molecules, (ii) inhibiting nitric oxide synthase-2 (NOS-2) expression and (iii) reducing the production of the pro-inflammatory cytokines interleukin-1beta (IL-1β) and interleukin-12 (IL-12p40). Taken together, these results point to the manipulation of the endocannabinoid system as a possible strategy to develop future MS therapeutic drugs.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The opioid and cannabinoid systems co-operate to regulate physiological processes such as nociception and reward. The endocannabinoid system may be a component of the brain reward circuitry and thus play a role not only in cannabinoid tolerance/dependence, but also in dependence/withdrawal for other misused drugs. We provide evidence of a cannabinoid mechanism in an animal model of morphine drug-seeking behaviour, referred to as behavioural sensitization. The present study was designed to test the effects of the CB1 cannabinoid receptor antagonist SR141716A in two different phases of morphine sensitization (induction and expression) and to measure the brain contents of arachidonoylethanolamide (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), the two main endogenous ligands for cannabinoid receptors in the different phases of morphine sensitization. The cannabinoid antagonist modified the signs of morphine sensitization when administered in the expression phase, whereas co-administration of SR141716A and morphine in the induction phase only slightly affected the behavioural responses, suggesting that CB1 receptor blockade attenuates the behavioural manifestations of morphine sensitization but not its development. AEA and 2-AG were affected differently by morphine during the two phases of behavioural sensitization. The alterations were in opposite directions and specific for the cerebral area analysed (caudate putamen, nucleus accumbens, hippocampus and prefrontal cortex). The results suggest that the endocannabinoid system undergoes profound changes during the different phases of sensitization to morphine in rats, providing a possible neurochemical basis for the previously observed cross-sensitization between opiates and cannabinoids.
    Type of Medium: Electronic Resource
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