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A dual inhibitor of FAAH and TRPV1 channels shows dose-dependent effect on depression-like behaviour in rats

Published online by Cambridge University Press:  12 December 2016

Christian Kirkedal ,
Gregers Wegener ,
Fabricio Moreira ,
Sâmia Regiane Lourenco Joca  and
Nico Liebenberg
Christian Kirkedal*
Affiliation:
Translational Neuropsychiatry Unit, Departments of Clinical Medicine, Aarhus University, RisskovDenmark
Gregers Wegener
Affiliation:
Translational Neuropsychiatry Unit, Departments of Clinical Medicine, Aarhus University, RisskovDenmark Center of Excellence for Pharmaceutical Sciences, North-West University (Potchefstroom Campus), Potchefstroom, South Africa
Fabricio Moreira
Affiliation:
Departament of Pharmacology, Federal University of Minas Gerais, MG, Brazil
Sâmia Regiane Lourenco Joca
Affiliation:
Translational Neuropsychiatry Unit, Departments of Clinical Medicine, Aarhus University, RisskovDenmark Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil
Nico Liebenberg
Affiliation:
Translational Neuropsychiatry Unit, Departments of Clinical Medicine, Aarhus University, RisskovDenmark
*
Christian Kirkedal, Translational Neuropsychiatric Unit, Departments of Clinical Medicine, Aarhus University, 8240, Risskov Denmark. Tel: +45 7847 1100; Fax: +45 7847 1108; E-mail: [email protected]
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Abstract

Objective

The cannabinoid receptor 1 (CB1) and transient receptor potential cation channel subfamily V member 1 (TRPV1) are proposed to mediate opposite behavioural responses. Their common denominator is the endocannabinoid ligand anandamide (AEA), which is believed to mediate antidepressant-like effect via CB1-R stimulation and depressive-like effect via TRPV1 activation. This is supposed to explain the bell-shaped dose-response curve for anandamide in preclinical models.

Methods

We investigated this assumption by administering the dual inhibitor of AEA hydrolysis and TRPV1 activation N-arachidonoyl-serotonin (AA-5HT) into the medial prefrontal cortex of rats. AA-5HT was given in three different doses (0.125, 0.250, 0.500 nmol/0.4 µl/side) and rat behaviour was assessed in the forced swim test.

Results

Our results show significant antidepressant-like effect of AA-5HT (0.250 nmol) but no effects of low or high doses. The effect of 0.250 nmol AA-5HT was partially attenuated when coadministering the inverse CB1-agonist rimonabant (1.6 µg).

Conclusion

A 0.250 nmol of AA-5HT administration into the medial prefrontal cortex induced a significant antidepressant-like effect that was partially attenuated by locally blocking CB1-receptor.

Keywords

cannabinoid receptor 1fatty acid amide hydrolaseforced swim testmedial prefrontal cortextrans potential vanilloid receptor 1
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 29 , Issue 6 , December 2017 , pp. 324 - 329
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Copyright
© Scandinavian College of Neuropsychopharmacology 2016 

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References

1. Holtzheimer, PE, Mayberg, HS. Stuck in a rut: rethinking depression and its treatment. Trends Neurosci 2011;34:1–9.CrossRefGoogle Scholar
2. Willner, P, Scheel-Kruger, J, Belzung, C. The neurobiology of depression and antidepressant action. Neurosci Biobehav Rev 2013;37(Pt 1):2331–2371.Google Scholar
3. Mezey, E, Toth, ZE, Cortright, DN et al. Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human. Proc Natl Acad Sci USA 2000;97:3655–3660.Google Scholar
4. Tsou, K, Brown, S, Sanudo-Pena, MC, Mackie, K, Walker, JM. Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience 1998;83:393–411.Google Scholar
5. Gobbi, G, Bambico, FR, Mangieri, R et al. Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis. Proc Natl Acad Sci USA 2005;102:18620–18625.CrossRefGoogle ScholarPubMed
6. Bambico, FR, Duranti, A, Nobrega, JN, Gobbi, G. The fatty acid amide hydrolase inhibitor URB597 modulates serotonin-dependent emotional behaviour, and serotonin 1A and serotonin 2A/C activity in the hippocampus. Eur Neuropsychopharmacol 2016;26.Google Scholar
7. McLaughlin, RJ, Hill, MN, Gorzalka, BB. A critical role for prefrontocortical endocannabinoid signaling in the regulation of stress and emotional behavior. Neurosci Biobehav Rev 2014;42:116–131.CrossRefGoogle ScholarPubMed
8. 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
9. Abdelhamid, RE, Kovács, KJ, Nunez, MG, Larson, AA. Depressive behavior in the forced swim test can be induced by TRPV1 receptor activity and is dependent on NMDA receptors. Pharmacol Res 2014;79:21–27.Google Scholar
10. Manna, SSS, Umathe, SN. A possible participation of transient receptor potential vanilloid type 1 channels in the antidepressant effect of fluoxetine. Eur J Pharmacol 2012;685:81–90.Google Scholar
11. Micale, V, Cristino, L, Tamburella, A et al. Anxiolytic effects in mice of a dual blocker of fatty acid amide hydrolase and transient receptor potential vanilloid type-1 channels. Neuropsychopharmacology 2009;34:593–606.CrossRefGoogle ScholarPubMed
12. You, I-J, Jung, Y-H, Kim, M-J et al. Alterations in the emotional and memory behavioral phenotypes of transient receptor potential vanilloid type 1-deficient mice are mediated by changes in expression of 5-HT1A, GABAA, and NMDA receptors. Neuropharmacology 2012;62:1034–1043.CrossRefGoogle ScholarPubMed
13. 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
14. Hillard, CJ. Biochemistry and pharmacology of the endocannabinoids arachidonylethanolamide and 2-arachidonylglycerol. Prostaglandins Other Lipid Mediat 2000;61:3–18.Google Scholar
15. Toth, A, Blumberg, PM, Boczan, J. Anandamide and the vanilloid receptor (TRPV1). Vitam Horm 2009;81:389–419.CrossRefGoogle ScholarPubMed
16. John, CS, Currie, PJ. N-arachidonoyl-serotonin in the basolateral amygdala increases anxiolytic behavior in the elevated plus maze. Behav Brain Res 2012;233:382–388.Google Scholar
17. Bambico, FR, Katz, N, Debonnel, G, Gobbi, G. Cannabinoids elicit antidepressant-like behavior and activate serotonergic neurons through the medial prefrontal cortex. J Neurosci 2007;27:11700–11711.Google Scholar
18. Paxinos, G, Watson, C. The rat brain, 7th edn. London, UK: Elsevier Inc, 2015.Google Scholar
19. Cryan, JF, Markou, A, Lucki, I. Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci 2002;23:238–245.CrossRefGoogle ScholarPubMed
20. Sartim, AG, Moreira, FA, Joca, SRL. Involvement of CB1 and TRPV1 receptors located in the ventral medial prefrontal cortex in the control of depressive-like behavior of rats submitted to the forced swimming test. Presented as a poster October 19th at Society of Neuroscience 2015, Chicago.Google Scholar
21. Navarria, A, Tamburella, A, Iannotti, FA et al. The dual blocker of FAAH/TRPV1 N-arachidonoylserotonin reverses the behavioral despair induced by stress in rats and modulates the HPA-axis. Pharmacol Res 2014;87:151–159.CrossRefGoogle ScholarPubMed
22. Kano, M. Control of synaptic function by endocannabinoid-mediated retrograde signaling. Proc Jpn Acad Ser B Phys Biol Sci 2014;90:235–250.CrossRefGoogle ScholarPubMed
23. Steiner, MA, Marsicano, G, Wotjak, CT, Lutz, B. Conditional cannabinoid receptor type 1 mutants reveal neuron subpopulation-specific effects on behavioral and neuroendocrine stress responses. Psychoneuroendocrinology 2008;33:1165–1170.Google Scholar