Brain TRPV1: a depressing TR(i)P down memory lane?

On sensory neurons, the capsaicin receptor TRPV1 (transient receptor potential, vanilloid subfamily, member 1) functions as a molecular integrator of noxious stimuli and represents a novel target for analgesic drugs. The presence of TRPV1 in the brain is now well established but, despite intensive research, its function is only beginning to be understood. New evidence implies an unexpected role for hippocampal TRPV1 in neuropsychiatric disorders. For instance, it was hypothesized that the effects of the cannabinoid-receptor antagonist rimonabant on mood might be due to its capability to antagonize TRPV1 receptors at high doses. Most studies, however, imply a positive (e.g. anxiolytic) outcome for TRPV1 antagonism. With potent small-molecule TRPV1 antagonists undergoing clinical trials, the effect of brain TRPV1 blockade might determine the future of this class of novel analgesic drugs. Clearly, more research is needed to delineate the biological role of brain TRPV1 receptors.