DOI: 10.1073/pnas.0509591102. Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis

Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis

10.1073/pnas.0509591102

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Although anecdotal reports suggest that cannabis may be used to alleviate symptoms of depression, the psychotropic effects and abuse liability of this drug prevent its therapeutic application. The active constituent of cannabis, Δ 9 -tetrahydrocannabinol, acts by binding to brain CB 1 cannabinoid receptors, but an alternative approach might be to develop agents that amplify the actions of endogenous cannabinoids by blocking their deactivation. Here, we show that URB597, a selective inhibitor of the enzyme fatty-acid amide hydrolase, which catalyzes the intracellular hydrolysis of the endocannabinoid anandamide, exerts potent antidepressant-like effects in the mouse tail-suspension test and the rat forced-swim test. Moreover, URB597 increases firing activity of serotonergic neurons in the dorsal raphe nucleus and noradrenergic neurons in the nucleus locus ceruleus. These actions are prevented by the CB 1 antagonist rimonabant, are accompanied by increased brain anandamide levels, and are maintained upon repeated URB597 administration. Unlike direct CB 1 agonists, URB597 does not exert rewarding effects in the conditioned place preference test or produce generalization to the discriminative effects of Δ 9 -tetrahydrocannabinol in rats. The findings support a role for anandamide in mood regulation and point to fatty-acid amide hydrolase as a previously uncharacterized target for antidepressant drugs.

Bibliography

Gobbi, G., Bambico, F. R., Mangieri, R., Bortolato, M., Campolongo, P., Solinas, M., Cassano, T., Morgese, M. G., Debonnel, G., Duranti, A., Tontini, A., Tarzia, G., Mor, M., Trezza, V., Goldberg, S. R., Cuomo, V., & Piomelli, D. (2005). Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis. Proceedings of the National Academy of Sciences, 102(51), 18620â18625.

Authors 17

G. Gobbi (first)
F. R. Bambico (additional)
R. Mangieri (additional)
M. Bortolato (additional)
P. Campolongo (additional)
M. Solinas (additional)
T. Cassano (additional)
M. G. Morgese (additional)
G. Debonnel (additional)
A. Duranti (additional)
A. Tontini (additional)
G. Tarzia (additional)
M. Mor (additional)
V. Trezza (additional)
S. R. Goldberg (additional)
V. Cuomo (additional)
D. Piomelli (additional)

References 39 Referenced 570

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Dates

Type	When
Created	19 years, 8 months ago (Dec. 13, 2005, 9:38 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 10:23 a.m.)
Indexed	22 minutes ago (Aug. 30, 2025, 3:14 a.m.)
Issued	19 years, 8 months ago (Dec. 13, 2005)
Published	19 years, 8 months ago (Dec. 13, 2005)
Published Online	19 years, 8 months ago (Dec. 13, 2005)
Published Print	19 years, 8 months ago (Dec. 20, 2005)

Funders 0

None

BibTeX

@article{Gobbi_2005, title={Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis}, volume={102}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0509591102}, DOI={10.1073/pnas.0509591102}, number={51}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Gobbi, G. and Bambico, F. R. and Mangieri, R. and Bortolato, M. and Campolongo, P. and Solinas, M. and Cassano, T. and Morgese, M. G. and Debonnel, G. and Duranti, A. and Tontini, A. and Tarzia, G. and Mor, M. and Trezza, V. and Goldberg, S. R. and Cuomo, V. and Piomelli, D.}, year={2005}, month=dec, pages={18620–18625} }

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