Δ9-tetrahydrocannabinol increases activity of tyrosine hydroxylase in cultured fetal mesencephalic neurons

Publisher Website
Google Scholar
Abstract
The exposure of pregnant rats to Δ9-tetrahydrocannabinol (Δ9-THC), the main psychoactive constituent ofCannabis sativa, during gestation and lactation, affects the gene expression and the activity of tyrosine hydroxylase (TH) in the brain of their offspring, measured at fetal and early postnatal ages, when the expression of this enzyme plays an important role in neural development. In the present article, we have examined whether Δ9-THC is able to affect TH activity in cultured mesencephalic neurons obtained from fetuses at gestational d 14. Thus, TH activity increased approximately twofold in cells obtained from naive fetuses when exposed for 24 h to medium containing Δ9-THC. In addition, TH activity was also approx twofold higher in cells obtained from fetuses exposed daily to Δ9-THC from d 5 of gestation than in cells obtained from control fetuses, when both were exposed to basal media. This effect of Δ9-THC on TH activity seems to be produced via the activation of cannabinoid receptors, in particular the CB1 subtype, which would presumably be located in these cells. This is because the exposure to medium containing both Δ9-THC and SR141716A, a specific antagonist for CB1 receptors, abolished the effect observed with Δ9-THC alone. SR141716A alone was without effect on TH activity. Collectively, our results support the notion that Δ9-THC increased TH activity in cultured mesencephalic neurons, as previously observed in vivo, and that this effect was produced by activation of CB1 receptors, which seem to be operative at these early ages. All this points to a role for the endogenous cannabimimetic system in brain development.