Reduced Anxiety, Conditioned Fear, and Hippocampal Long-Term Potentiation in Transient Receptor Potential Vanilloid Type 1 Receptor-Deficient Mice

Abstract

The transient receptor potential vanilloid type 1 channel (TRPV1) (formerly called vanilloid receptor VR1) is known for its key role of functions in sensory nerves such as perception of inflammatory and thermal pain. Much less is known about the physiological significance of the TRPV1 expression in the brain. Here we demonstrate that TRPV1 knock-out mice (TRPV1-KO) show less anxiety-related behavior in the light-dark test and in the elevated plus maze than their wild-type littermates with no differences in locomotion. Furthermore, TRPV1-KO mice showed less freezing to a tone after auditory fear conditioning and stress sensitization. This reduction of conditioned and sensitized fear could not be explained by alterations in nociception. Also, tone perception per se was unaffected, as revealed by determination of auditory thresholds through auditory brainstem responses and distortion-product otoacoustic emissions. TRPV1-KO showed also less contextual fear if assessed 1 d or 1 month after strong conditioning protocols. These impairments in hippocampusdependent learning were mirrored by a decrease in long-term potentiation in the Schaffer collateral-commissural pathway to CA1 hippocampal neurons. Our data provide first evidence for fear-promoting effects of TRPV1 with respect to both innate and conditioned fear and for a decisive role of this receptor in synaptic plasticity.

The Expression Pattern of TRPV1 in Brain

“…Moreover, Marsch et al (2007) showed that TRPV1 was involved in hippocampal synaptic plasticity using TRPV1 knock-out, and Gibson et al (2008) confirmed this finding by showing that capsaicin and capsazepine, respectively, induced and repressed hippocampal longterm depression (LTD). Nevertheless, Cavanaugh et al (2011) could not detect any TRPV1 expression in these two structures.…”

Oxytocin Stimulates Extracellular Ca2+ Influx Through TRPV2 Channels in Hypothalamic Neurons to Exert Its Anxiolytic Effects

“…In contrast to the anxiolytic effect of TRPV2 in the PVN, however, TRPC5 seems to be anxiogenic in the amygdala, as TRPC5 −/− mice exhibit diminished innate fear in tests for general and social anxiety (Riccio et al, 2009). Likewise, TRPV1 knockout mice show decreased anxiety-like behavior in the LDB and EPM, as well as reduced conditioned fear, suggesting that TRPV1 activity promotes anxiogenic behavior (Marsch et al, 2007). In summary, our in vivo and in vitro studies identified TRPV2 channels in the PVN of rats as mediators of OXTinduced anxiolysis.…”

Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex

“…The TRPV1 antagonist capsazepine reversed the decline in 5-HT excitation induced by high WIN55,2212-2 doses. Interestingly, TRPV1 is expressed in both DR and PFC (Liapi and Wood, 2005) and is implicated in anxiety, conditioned fear, and hippocampal long-term potentiation (Marsch et al, 2007) and in schizophrenia (Chahl, 2007), whose negative symptoms overlap with depression. Second, we consider the possible role of the putative CB 3 R or a non-CB 1 cannabinoid receptor possessing a lower affinity to WIN55,212-2 proposed to be present in glutamatergic terminals and thus in a position to inhibit the release of excitatory amino acids (Hajos and Freund, 2002).…”