Effects of cannabinoids on catecholamine uptake and release in hypothalamic and striatal synaptosomes

In vitro effects of delta 9-tetrahydrocannabinol (delta 9-THC), delta 8-tetrahydrocannabinol (delta 8-THC), cannabinol (CBN) and cannabidiol (CBD) have been studied on the uptake and release of 3H-labeled dopamine (DA) and norepinephrine (NE) in the synaptosomal preparation of rat brain corpus striatum and hypothalamus. The uptake of both DA and NE in these two regions was stimulated at low concentrations of delta 9-THC (1 x 10(-7) and 2 x 10(-7) M) and delta 8-THC (5 x 10(-9) and 1 x 10(-8) M), whereas at higher concentrations (1 x 10(-5) and 1 x 10(-4) M) both delta 9-THC and its delta 8-isomer inhibited the uptake of DA and NE. Similarly, the release of DA and NE from the preloaded synaptosomes of these two brain regions were inhibited at low concentrations of delta 9-THC (1 x 10(-7) M) and delta 8-THC (1 x 10(-8) M) and stimulated at high concentrations of both isomers (1 x 10(-5) and 1 x 10(-4) M). High concentrations of both CBN and CBD were needed to produce only an inhibitory effect on the uptake and the stimulation on the release of DA and NE in synaptosomes of the two brain regions. No significant effect was found at lower concentrations of CBN and CBD. These results demonstrate that 1) delta 9- and delta 8-THC, but not CBN and CBD, produce a biphasic effect on the uptake and release of DA and NE in the corpus striatum and hypothalamic regions of brain and 2) delta 8-THC is more potent than delta 9-THC on both uptake and release of DA and NE in these two brain regions.