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Involvement of TRPV1 channels in the periaqueductal grey on the modulation of innate fear responses

Published online by Cambridge University Press:  22 December 2014

Daniele C. Aguiar ,
Ana F. Almeida-Santos ,
Fabricio A. Moreira  and
Francisco S. Guimarães
Daniele C. Aguiar*
Affiliation:
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
Ana F. Almeida-Santos
Affiliation:
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
Fabricio A. Moreira
Affiliation:
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
Francisco S. Guimarães
Affiliation:
Department of Pharmacology, Ribeirao Preto School of Medicine, Universidade de São Paulo, Ribeirão Preto - SP, Brazil
*
Daniele C Aguiar, Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. Tel: +55 31 3409 2718; Fax: +55 31 3409 2695; E-mail: danieleaguiar@ufmg.br
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Abstract

Objectives

The transient receptor potential vanilloid type-1 channel (TRPV1) is expressed in the midbrain periaqueductal grey (PAG), a region of the brain related to aversive responses. TRPV1 antagonism in the dorsolateral PAG (dlPAG) induces anxiolytic-like effects in models based on conflict situations. No study, however, has investigated whether these receptors could contribute to fear responses to proximal threat. Thus, we tested the hypothesis that TRPV1 in the PAG could mediate fear response in rats exposed to a predator.

Methods

We verified whether exposure to a live cat (a natural predator) would activate TRPV1-expressing neurons in the PAG. Double-staining immunohistochemistry was used as a technique to detect c-Fos, a marker of neuronal activation, and TRPV1 expression. We also investigated whether intra-dlPAG injections of the TRPV1 antagonist, capsazepine (CPZ), would attenuate the behavioural consequences of predator exposure.

Results

Exposure to a cat increased c-Fos expression in TRPV1-positive neurons, mainly in the dorsal columns of the PAG, suggesting that TRPV1-expressing neurons are activated by threatening stimuli. Accordingly, local injection of CPZ inhibited the fear responses.

Conclusion

These data support the hypothesis that TRPV1 channels mediate fear reactions in the dlPAG. This may have an implication for the development of TRPV1-antagonists as potential drugs for the treatment of certain psychiatric disorders.

Keywords

defensive behaviourTRPV1vanilloid
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 27 , Issue 2 , April 2015 , pp. 97 - 105
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Copyright
© Scandinavian College of Neuropsychopharmacology 2014 

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References

1. Blanchard, RJ, Blanchard, DC. Antipredator defensive behaviors in a visible burrow system. J Comp Psychol 1989;103:70–82.CrossRefGoogle Scholar
2. Blanchard, RJ, Blanchard, DC, Rodgers, J, Weiss, SM. The characterization and modelling of antipredator defensive behavior. Neurosci Biobehav Rev 1990;14:463–472.CrossRefGoogle ScholarPubMed
3. Canteras, NS, Blanchard, DC. A behavioral and neural systems comparison of unconditioned and conditioned defensive behavior. In: RJ Blanchard, DC Blanchard, G Griebel and D Nutt, editors. Handbook of anxiety and fear. Amsterdan: Elsevier, 2008; pp. 141–154.CrossRefGoogle Scholar
4. Blanchard, DC, Blanchard, RJ. Defensive behaviors, fear and anxiety, 1st edn. In: RJ Blanchard, DC Blanchard, G Griebel and D Nutt, editors. Handbook of anxiety and fear. Amsterdam: Elsevier, 2008; pp. 63–99.CrossRefGoogle Scholar
5. Beijamini, V, Guimaraes, FS. c-Fos expression increase in NADPH-diaphorase positive neurons after exposure to a live cat. Behav Brain Res 2006;170:52–61.CrossRefGoogle ScholarPubMed
6. Canteras, NS, Chiavegatto, S, Valle, LE, Swanson, LW. Severe reduction of rat defensive behavior to a predator by discrete hypothalamic chemical lesions. Brain Res Bull 1997;44:297–305.CrossRefGoogle ScholarPubMed
7. Canteras, NS, Goto, M. Fos-like immunoreactivity in the periaqueductal gray of rats exposed to a natural predator. Neuroreport 1999;10:413–418.CrossRefGoogle ScholarPubMed
8. Blanchard, DC, Canteras, NS, Markham, CM, Pentkowski, NS, Blanchard, RJ. Lesions of structures showing FOS expression to cat presentation: effects on responsivity to a cat, cat odor, and nonpredator threat. Neurosci Biobehav Rev 2005;29:1243–1253.CrossRefGoogle ScholarPubMed
9. McNaughton, N, Corr, PJ. A two-dimensional neuropsychology of defense: fear/anxiety and defensive distance. Neurosci Biobehav Rev 2004;28:285–305.CrossRefGoogle ScholarPubMed
10. Graeff, FG. Serotonin, the periaqueductal gray and panic. Neurosci Biobehav Rev 2004;28:239–259.CrossRefGoogle ScholarPubMed
11. Adamec, RE, Burton, P, Shallow, T, Budgell, J. NMDA receptors mediate lasting increases in anxiety-like behavior produced by the stress of predator exposure – implications for anxiety associated with posttraumatic stress disorder. Physiol Behav 1999;65:723–737.CrossRefGoogle ScholarPubMed
12. Blanchard, DC, Blanchard, RJ, Carobrez Ade, P, Veniegas, R, Rodgers, RJ, Shepherd, JK. MK-801 produces a reduction in anxiety-related antipredator defensiveness in male and female rats and a gender-dependent increase in locomotor behavior. Psychopharmacology (Berl) 1992;108:352–362.CrossRefGoogle Scholar
13. McGregor, IS, Hargreaves, GA, Apfelbach, R, Hunt, GE. Neural correlates of cat odor-induced anxiety in rats: region-specific effects of the benzodiazepine midazolam. J Neurosci 2004;24:4134–4144.CrossRefGoogle ScholarPubMed
14. Moreira, FA, Guimaraes, FG. Lack of effects of clomipramine on Fos and NADPH-diaphorase double-staining in the periaqueductal gray after exposure to an innate fear stimulus. Physiol Behav 2008;94:316–321.CrossRefGoogle Scholar
15. Aguiar, DC, Guimaraes, FS. Blockade of NMDA receptors and nitric oxide synthesis in the dorsolateral periaqueductal gray attenuates behavioral and cellular responses of rats exposed to a live predator. J Neurosci Res 2009;87:2418–2429.CrossRefGoogle ScholarPubMed
16. Di Marzo, V, Bisogno, T, De Petrocellis, L. Anandamide: some like it hot. Trends Pharmacol Sci 2001;22:346–349.CrossRefGoogle ScholarPubMed
17. Holzer, P. Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev 1991;43:143–201.Google ScholarPubMed
18. Acs, G, Palkovits, M, Blumberg, PM. [3H]resiniferatoxin binding by the human vanilloid (capsaicin) receptor. Brain Res Mol Brain Res 1994;23:185–190.CrossRefGoogle ScholarPubMed
19. Szallasi, A, Blumberg, PM. Characterization of vanilloid receptors in the dorsal horn of pig spinal cord. Brain Res 1991;547:335–338.CrossRefGoogle ScholarPubMed
20. Toth, A, Boczan, J, Kedei, N et al. Expression and distribution of vanilloid receptor 1 (TRPV1) in the adult rat brain. Brain Res Mol Brain Res 2005;135:162–168.CrossRefGoogle ScholarPubMed
21. Toth, A, Kedei, N, Wang, Y, Blumberg, PM. Arachidonyl dopamine as a ligand for the vanilloid receptor VR1 of the rat. Life Sci 2003;73:487–498.CrossRefGoogle ScholarPubMed
22. Huang, SM, Bisogno, T, Trevisani, M et al. An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors. Proc Natl Acad Sci U S A 2002;99:8400–8405.CrossRefGoogle ScholarPubMed
23. Chu, CJ, Huang, SM, De Petrocellis, L et al. N-oleoyldopamine, a novel endogenous capsaicin-like lipid that produces hyperalgesia. J Biol Chem 2003;278:13633–13639.CrossRefGoogle ScholarPubMed
24. Hwang, SW, Cho, H, Kwak, J et al. Direct activation of capsaicin receptors by products of lipoxygenases: endogenous capsaicin-like substances. Proc Natl Acad Sci U S A 2000;97:6155–6160.CrossRefGoogle ScholarPubMed
25. Kasckow, JW, Mulchahey, JJ, Geracioti, TD. Effects of the vanilloid agonist olvanil and antagonist capsazepine on rat behaviors. Prog Neuropsychopharmacol Biol Psychiatry 2004;28:291–295.CrossRefGoogle ScholarPubMed
26. Marsch, R, Foeller, E, Rammes, G et al. Reduced anxiety, conditioned fear, and hippocampal long-term potentiation in transient receptor potential vanilloid type 1 receptor-deficient mice. J Neurosci 2007;27:832–839.CrossRefGoogle ScholarPubMed
27. Aguiar, DC, Terzian, AL, Guimaraes, FS, Moreira, FA. Anxiolytic-like effects induced by blockade of transient receptor potential vanilloid type 1 (TRPV1) channels in the medial prefrontal cortex of rats. Psychopharmacology (Berl) 2009;205:217–225.CrossRefGoogle ScholarPubMed
28. Santos, CJ, Stern, CA, Bertoglio, LJ. Attenuation of anxiety-related behaviour after the antagonism of transient receptor potential vanilloid type 1 channels in the rat ventral hippocampus. Behav Pharmacol 2008;19:357–360.CrossRefGoogle ScholarPubMed
29. Terzian, AL, Aguiar, DC, Guimaraes, FS, Moreira, FA. Modulation of anxiety-like behaviour by transient receptor potential vanilloid Type 1 (TRPV1) channels located in the dorsolateral periaqueductal gray. Eur Neuropsychopharmacol 2009;19:188–195.CrossRefGoogle ScholarPubMed
30. Rubino, T, Realini, N, Castiglioni, C et al. Role in anxiety behavior of the endocannabinoid system in the prefrontal cortex. Cereb Cortex 2008;18:1292–1301.CrossRefGoogle ScholarPubMed
31. Lisboa, SF, Camargo, LH, Magesto, AC, Resstel, LB, Guimaraes, FS. Cannabinoid modulation of predator fear: involvement of the dorsolateral periaqueductal gray. Int J Neuropsychopharmacol 2014;17:1193–1206.CrossRefGoogle ScholarPubMed
32. Cassaroto, P, Terzian, AL, Aguiar, DC et al. Opposing roles for cannabinoid receptor type-1 (CB1) and transient receptor potential vanilloid type-1 channel (TRPV1) on the modulation of panic-like responses in rats. Neuropsychopharmacology 2012;37:478–486.CrossRefGoogle Scholar
33. Paxinos, G, Watson, C. The rat brain in stereotaxic coordinates, 3rd edn. New York: Academic Press, 1997.Google Scholar
34. Paxinos, G, Watson, C. The rat brain in stereotaxic coordinates, 6th edn. London: Academic Press/Elsevier, 2007.Google Scholar
35. Beijamini, V, Guimaraes, FS. Activation of neurons containing the enzyme nitric oxide synthase following exposure to an elevated plus maze. Brain Res Bull 2006;69:347–355.CrossRefGoogle Scholar
36. De Oliveira, RM, Del Bel, EA, Guimaraes, FS. Effects of excitatory amino acids and nitric oxide on flight behavior elicited from the dorsolateral periaqueductal gray. Neurosci Biobehav Rev 2001;25:679–685.CrossRefGoogle ScholarPubMed
37. Dielenberg, RA, Hunt, GE, McGregor, IS. ‘When a rat smells a cat’: the distribution of Fos immunoreactivity in rat brain following exposure to a predatory odor. Neuroscience 2001;104:1085–1097.CrossRefGoogle Scholar
38. Cullinan, WE, Herman, JP, Battaglia, DF, Akil, H, Watson, SJ. Pattern and time course of immediate early gene expression in rat brain following acute stress. Neuroscience 1995;64:477–505.CrossRefGoogle ScholarPubMed
39. Nagahara, AH, Handa, RJ. Age-related changes in c-fos mRNA induction after open-field exposure in the rat brain. Neurobiol Aging 1997;18:45–55.CrossRefGoogle ScholarPubMed
40. Campeau, S, Falls, WA, Cullinan, WE, Helmreich, DL, Davis, M, Watson, SJ. Elicitation and reduction of fear: behavioural and neuroendocrine indices and brain induction of the immediate-early gene c-fos. Neuroscience 1997;78:1087–1104.CrossRefGoogle ScholarPubMed
41. Campeau, S, Akil, H, Watson, SJ. Lesions of the medial geniculate nuclei specifically block corticosterone release and induction of c-fos mRNA in the forebrain associated with audiogenic stress in rats. J Neurosci 1997;17:5979–5992.CrossRefGoogle ScholarPubMed
42. Singewald, N, Sharp, T. Neuroanatomical targets of anxiogenic drugs in the hindbrain as revealed by Fos immunocytochemistry. Neuroscience 2000;98:759–770.CrossRefGoogle ScholarPubMed
43. Casarotto, PC, Terzian, AL, Aguiar, DC et al. Opposing roles for cannabinoid receptor type-1 (CB(1)) and transient receptor potential vanilloid type-1 channel (TRPV1) on the modulation of panic-like responses in rats. Neuropsychopharmacology 2012;37:478–486.CrossRefGoogle Scholar
44. Moreira, FA, Aguiar, DC, Terzian, AL, Guimaraes, FS, Wotjak, CT. Cannabinoid type 1 receptors and transient receptor potential vanilloid type 1 channels in fear and anxiety-two sides of one coin? Neuroscience 2012;204:186–192.CrossRefGoogle ScholarPubMed
45. Micale, V, Di Marzo, V, Sulcova, A, Wotjak, CT, Drago, F. Endocannabinoid system and mood disorders: priming a target for new therapies. Pharmacol Ther 2013;138:18–37.CrossRefGoogle ScholarPubMed
46. Li, HB, Mao, RR, Zhang, JC, Yang, Y, Cao, J, Xu, L. Antistress effect of TRPV1 channel on synaptic plasticity and spatial memory. Biol Psychiatry 2008;64:286–292.CrossRefGoogle ScholarPubMed
47. Starowicz, K, Nigam, S, Di Marzo, V. Biochemistry and pharmacology of endovanilloids. Pharmacol Ther 2007;114:13–33.CrossRefGoogle Scholar
48. Chavez, AE, Chiu, CQ, Castillo, PE. TRPV1 activation by endogenous anandamide triggers postsynaptic long-term depression in dentate gyrus. Nat Neurosci 2010;13:1511–1518.CrossRefGoogle ScholarPubMed
49. Grueter, BA, Brasnjo, G, Malenka, RC. Postsynaptic TRPV1 triggers cell type-specific long-term depression in the nucleus accumbens. Nat Neurosci 2010;13:1519–1525.CrossRefGoogle ScholarPubMed
50. Di Marzo, V. Targeting the endocannabinoid system: to enhance or reduce? Nat Rev Drug Discov 2008;7:438–455.CrossRefGoogle ScholarPubMed