When Delta(9)-tetrahydrocannabinol (Delta(9)-THC,15 mg/kg) was injected intraperitoneally twice a day for 6 days, tolerance to its analgesic effect appeared to be complete. Chronic exposure to Delta(9)-THC caused a significant reduction in CB1 receptor binding in all brain areas that contain this receptor. Cannabinoid receptor density was markedly reduced in the cerebellum (52%), hippocampus (40%) and globus pallidum (47%) compared to 30% in the cortex and striatum. Chronic exposure enhanced the cAMP pathway, as shown by the significant increase of cAMP levels and PKA activity in the areas with receptor down-regulation (cerebellum, striatum and cortex). We propose that the increase in cAMP cascade is part of the biochemical basis of cannabinoid tolerance
Rubino, T., Viganò, D., Massi, P., Spinello, M., Zagato, E., Giagnoni, G., et al. (2000). Chronic Δ-9-tetrahydrocannabinol treatment increases cAMP levels and cAMP-dependent protein kinase activity in some rat brain regions. NEUROPHARMACOLOGY, 39(7), 1331-1336 [10.1016/S0028-3908(99)00196-3].
Chronic Δ-9-tetrahydrocannabinol treatment increases cAMP levels and cAMP-dependent protein kinase activity in some rat brain regions
Giagnoni, G;
2000
Abstract
When Delta(9)-tetrahydrocannabinol (Delta(9)-THC,15 mg/kg) was injected intraperitoneally twice a day for 6 days, tolerance to its analgesic effect appeared to be complete. Chronic exposure to Delta(9)-THC caused a significant reduction in CB1 receptor binding in all brain areas that contain this receptor. Cannabinoid receptor density was markedly reduced in the cerebellum (52%), hippocampus (40%) and globus pallidum (47%) compared to 30% in the cortex and striatum. Chronic exposure enhanced the cAMP pathway, as shown by the significant increase of cAMP levels and PKA activity in the areas with receptor down-regulation (cerebellum, striatum and cortex). We propose that the increase in cAMP cascade is part of the biochemical basis of cannabinoid tolerance
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