Synthetic cannabinoid JWH-210 induces motor impairments through the regulation of neurotrans- mission in tetanus toxin-treated mice

The problem of new psychoactive substances is emerging globally. Cannabinoid receptors mediate the action of synthetic cannabinoids, which are one of most abused drugs. Recently, cannabinoid receptors 1 (CB1R) have been reported to silence glutamatergic nerve terminals in cerebellar granule cells via synaptic vesicle redistribution. This study aimed to determine whether synthetic cannabinoid administration (0.1 mg/kg, 5 days) influences the development of biotoxin-induced deficit in neuronal homeostasis. We observed that JWH-210, a synthetic cannabinoid, induced motor impairment and decrement of vesicle-associated membrane proteins 2 (VAMP2) levels in the cerebellum of mice treated with tetanus toxin. Cerebellar glutamatergic neuronal homeostasis was hampered by JWH-210 administration, as evidenced by increased glutamate concentration levels in the cerebellum of the tetanus-treated mice. However, JWH-250, which has a lower CB1R binding affinity than does JWH-210 (Ki value: 1.1 × 10–7 M, and 2.6 × 10–8 M, respectively) did not exacerbate motor impairment and VMAP2 decrements in the cerebellum of tetanus-treated mice. In addition, tyrosine hydroxylase, the dopamine synthetic enzyme was downregulated in the striatum of JWH-210/Tetanus mice. These results suggest that JWH210 may have an additive effect on the tetanus toxin-induced glutamatergic and dopaminergic neuronal dysfunction. PM292 Possible involvement of cannabinoid CB1 receptors in behavioral impairments after withdrawal from chronic methamphetamine administration in mice. Ryo Fukumori1, Catherine Ledent2, Satoshi Yamada1, Taku Yamaguchi1, Tsuneyuki Yamamoto1 1Nagasaki International University, Japan, 2Université Libre de