Abstract
Rationale
Contextual fear is evoked by re-exposing an animal to an environment that has been previously paired with an aversive or unpleasant stimulus. It can be assessed by freezing and cardiovascular changes such as increase in mean arterial pressure and heart rate. A marked increase in neuronal activity is associated with contextual fear conditioning, especially in limbic structures involved with defense reactions, such as the ventral portion of medial prefrontal cortex.
Objective
Given the fact that transient receptor potential vanilloid type 1 (TRPV1) receptors could be involved in the expression of defensive behavior, the present work tested the hypothesis that TRPV1 manipulation in the ventromedial prefrontal cortex (vMPFC) modulates the expression of contextual conditioned fear.
Methods
Male Wistar rats received bilateral microinjections into the vMPFC of the TRPV1 receptor antagonists capsazepine (1, 10, and 60 nmol/200 nL) or 6-iodonordihydrocapsaicin (3 nmol/200 nL), and the TRPV1 agonist capsaicin (1 nmol/200 nL) preceded by vehicle or 6-iodonordihydrocapsaicin before re-exposure to the experimental chamber for 10 min, 48 h after conditioning in two different protocols distinct by their aversiveness.
Results
Both antagonists reduced the freezing and cardiovascular responses in the high aversive protocol. Capsaicin caused an increase in fear-associated responses that could be blocked by 6-iodonordihydrocapsaicin.
Conclusions
Our results indicate that TRPV1 receptors located in the vMPFC have a tonic involvement in the modulation of the expression of contextual fear conditioning.




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Acknowledgments
The authors wish to thank I.A.C. Fortunato and J.C. Aguiar for the technical help. A.L. Terzian is supported by the CNPq scholarship (process 290008/2009-3). This research was supported by grants from FAPESP (2011/07332-3), CNPq, and FAEPA.
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The authors declare no conflicts of interests.
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Terzian, A.L.B., dos Reis, D.G., Guimarães, F.S. et al. Medial prefrontal cortex Transient Receptor Potential Vanilloid Type 1 (TRPV1) in the expression of contextual fear conditioning in Wistar rats. Psychopharmacology 231, 149–157 (2014). https://doi.org/10.1007/s00213-013-3211-9
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DOI: https://doi.org/10.1007/s00213-013-3211-9