Presynaptic TRPV1 vanilloid receptor function is age- but not CB1 cannabinoid receptor-dependent in the rodent forebrain.

Abstract Neocortical and striatal TRPV 1 (vanilloid or capsaicin) receptors (TRPV 1 Rs) are excitatory ligand-gated ion channels, and are implicated in psychiatric disorders. However, the purported presynaptic neuromodulator role of TRPV 1 Rs in glutamatergic, serotonergic or dopaminergic terminals of the rodent forebrain remains little understood. With the help of patch-clamp electrophysiology and neurochemical approaches, we mapped the age-dependence of presynaptic TRPV 1 R function, and furthermore, we aimed at exploring whether the presence of CB 1 cannabinoid receptors (CB 1 Rs) influences the function of the TRPV 1 Rs, as both receptor types share endogenous ligands. We found that the major factor which affects presynaptic TRPV 1 R function is age: by post-natal day 13, the amplitude of capsaicin-induced release of dopamine and glutamate is halved in the rat striatum, and two weeks later, capsaicin already loses its effect. However, TRPV 1 R receptor function is not enhanced by chemical or genetic ablation of the CB 1 Rs in dopaminergic, glutamatergic and serotonergic terminals of the mouse brain. Altogether, our data indicate a possible neurodevelopmental role for presynaptic TRPV 1 Rs in the rodent brain, but we found no cross-talk between TRPV 1 Rs and CB 1 Rs in the same nerve terminal.