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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: Christian.kirkedal@clin.au.dk
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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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