Pregnenolone is considered the inactive precursor of all steroid hormones and its potential functional effects have been largely neglected. The administration of the main active principle of Cannabis sativa (marijuana) Δ9-tetrahydrocannabinol (THC) substantially increases the synthesis of pregnenolone in the brain via the activation of type-1 cannabinoid (CB1) receptor. Pregnenolone then, acting as a signaling specific inhibitor of the CB1 receptor, reduces several effects of THC. This negative feedback mediated by pregnenolone reveals an unknown paracrine/autocrine loop protecting the brain from CB1 receptor over-activation that could open an unforeseen novel approach for the treatment of cannabis intoxication and addiction.

Numerous research has pointed out that serotonin2c (5-HT 2C ) receptor, a subtype of 5-HT receptors belonging to the G-protein-coupled receptor superfamily, modulates the activity of mesencephalic dopamine (DA) neurons, the dysfunction of which is involved in devastating diseases such as schizophrenia, Parkinson's disease, and drug addiction. In the present study, using in vivo intracerebral microdialysis and Chinese hamster ovary (CHO) cells expressing 5-HT 2C receptors to identify appropriate 5-HT 2C receptor ligands, we sought to determine whether the property of 5-HT 2C receptors to spontaneously activate intracellular signaling pathways in vitro (constitutive activity) participates in the tonic inhibitory control that they exert on DA release in the rat striatum and nucleus accumbens in vivo. In

BackgroundHuntington's disease (HD) is a fatal inherited neurodegenerative disease, caused by a