The effects of (-)-Δ9-THC were studied on the release and accumulation of 3H5HT and 3HNE in a rat forebrain synaptosomal preparation. These studies were designed to evaluate the possible sites of action of Δ9-THC on these two processes. Δ9-THC inhibited the accumulation of 3H-leucine, 3HNE, and 3H5HT, as well as facilitated the release of the latter two amines (to a lesser degree), but had no effect on the release of 3H-leucine. Eighteen-hour pre-treatment with reserpine diminished the ability of Δ9-THC to induce release of 3H5HT, but had no effect on the in vitro inhibition of synaptosomal uptake of this amine. Concentrations of Δ9-THC which blocked the uptake of 3H5HT also reduced the conversion of 3H5HT to 3H-5-hydroxy-3-indoleacetic acid. However, Δ9-THC, at concentrations which facilitated release of 3H5HT from preloaded synaptosomes, increased the amount of 3H5HIAA found in the medium. Taken together, these data suggest that Δ9-THC facilitates release from the synaptic vesicle and retards accumulation at the neuronal membrane.
ASJC Scopus subject areas