Effect of delta9-tetrahydrocannabinol on the synthesis of dopamine and norepinephrine in mouse brain synaptosomes.
The effects of delta 9-tetrahydrocannabinol (THC) on the conversion of [3H]tyrosine (TYR) to [3H]dopamine (DA) and [3H]norepinephrine (NE) by mouse brain synaptosomes were studied. The active uptake of TYR and its conversion to DA and NE were found to be concentrated in a synaptosomal subfraction prepared by using differential and density gradient centrifugation. Therefore, drug studies were performed by using the less pure P2 fraction. THC was administered in vitro by using a polyvinylpyrrolidone vehicle. DA synthesis was examined both in synaptosomes prepared from whole brain and from corpus striatum. THC produced increases in the conversion of TYR to DA in both preparations. Synthesis was stimulated maximally by 10 microns THC in both preparations. Higher concentrations produced either no further increase (whole brain) or a decrease in the synthesis of DA. NE synthesis was measured in synaptosomes prepared from whole brain and from brainstem. A concentration-dependent biphasic response was observed in both preparations. Peak increases in NE synthesis were observed with a 10 micron concentration of THC in synaptosomes from whole brain and a 3 micro concentration in the brainstem. THC also inhibited the active uptake of TYR into synaptosomes in all preparations studied. The lC50 in whole brain was 12.2 microns. The decrease in precursor uptake may be the cause of the decreased DA and NE synthesis observed at the higher concentrations of THC. The data from these studies suggest that delta 9-THC can have a direct effect upon catecholamine-containing neurons in the brain.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis*; D013759:Dronabinol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009638:Norepinephrine / Q000096:biosynthesis*; D013347:Subcellular Fractions / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D014443:Tyrosine; D013759:Dronabinol; D004298:Dopamine; D009638:Norepinephrine