Modulation of defensive behavior by Transient Receptor Potential Vanilloid Type-1 (TRPV1) Channels

• TRPV1-containing neurons are expressed in defensive-related brain regions.
• TRPV1 antagonists induce anti-panic and anxiolytic effects.
• Endovanilloids interact with endocannabinoids and nitric oxide to control anxiety.

The Transient Receptor Potential Vanilloid Type-1 (TRPV1) was first characterized in primary afferent fibers as a receptor for capsaicin (the pungent ingredient of chili peppers). Later on, this cation-permeable ion channel was also described in the central nervous system, where its main putative endogenous ligand is N-arachidonoyl ethanolamide (an endocannabinoid, also known as anandamide). Recent results employing genetic, pharmacological and histochemical techniques indicate that TRPV1 tonically modulate anxiety, fear and panic responses in brain regions related to defensive responses, such as the dorsal periaqueductal gray, the hippocampus and the medial prefrontal cortex. Genetic deletion or antagonism of this ion channel induces anxiolytic-like effects in several animal models. The main mechanism responsible for TRPV1-mediated effects on anxiety seems to involve facilitation of glutamatergic neurotransmission. In addition, there is evidence for interactions with other neurotransmitter systems, such as nitric oxide and endocannabinoids.

Figure optionsDownload as PowerPoint slide