Locomotor effects, anandamide

Cannabinoid receptor agonists stimulate the production and release of nitric oxide (NO) by a CBi receptor-mediated mechanism utilizing one of the NO synthase (NOS) isoforms in neuronal tissues and model cells (see Fimiani et al. 1999a for review). The signal transduction pathway between CBi receptors and neuronal NOS (nNOS) regulation is believed to be important for mediating the effects of A -THC on hypothermia and locomotor activity (but not antinociception), as determined by the absence of these responses in nNOS (-/-) knock-out mice (Azad et al. 2001). NO production was stimulated by anandamide via SR141716-sensitive CBl receptors in rat median eminence shces, but it was not clear from these studies... 

Anandamide produces the full range of behavioral effects (antinociception, catalepsy, and impaired locomotor activity) in CBi receptor knockout mice (Di Marzo et al. 2000). Furthermore, anandamide-stimulated GTPyS activity can be elicited in brain membranes from these mice (Breivogel et al. 2001). These effects were not sensitive to inhibition by SR141716A. Interestingly, of all cannabinoid ligands tested, only WIN 55,212-2 elicited GTPyS activity in CBi knockout mice. This same phenomenon has also been demonstrated in a second strain of CBi receptor knockout mice (Monory et al. 2002). 

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