Correction for Gobbi et al., Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis

By G. Gobbi, F. Bambico, R. Mangieri, M. Bortolato, P. Campolongo, M. Solinas, T. Cassano, M. Morgese, G. Debonnel, A. Duranti and 7 more. Proceedings of the National Academy of Sciences of the United States of America, 2005

685 citations recorded by the source corpus.

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, delta9-tetrahydrocannabinol, acts by binding to brain CB1 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 CB1 antagonist rimonabant, are accompanied by increased brain anandamide levels, and are maintained upon repeated URB597 administration. Unlike direct CB1 agonists, URB597 does not exert rewarding effects in the conditioned place preference test or produce generalization to the discriminative effects of delta9-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.

Subfields: Cellular and Molecular Neuroscience, Pharmacology, Plant Science

View Paper: https://www.semanticscholar.org/paper/eef3f50eb07a6ed605cc993d57a6c1b4b91b3800

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. L. Parker
2. Tamás F. Freund
3. I. Katona
4. P. Pacher
5. S. Batkai
6. George Kunos
7. R. Mechoulam
8. György Buzsáki

In Pharmacology

1. Tamás F. Freund
2. L. Parker
3. I. Katona
4. P. Pacher
5. S. Batkai
6. George Kunos
7. R. Mechoulam
8. V. Di Marzo

In Plant Science

1. Tamás F. Freund

Citations in the corpus

• Endocannabinoid signaling as a synaptic circuit breaker in neurological disease (2008, background): “Anandamide is already well known, and a selective inhibitor of its degrading enzyme, FAAH, has shown its potential as an anxiolytic, antidepressant and antinociceptive compoun”
• The Endocannabinoid System as an Emerging Target of Pharmacotherapy (2006, background): “…al., 2006), and the amplification of the actions of endocannabinoids by the FAAH inhibitor URB597 was found to produce antidepressant-like effects in the mouse tailsuspension and rat forced-swim tests, without eliciting reward-related effects indicative of addictive potential (Gobbi et al., 2005).”
• The endocannabinoid system and the brain. (2013, background): “…of the developing brain (Buckley et al. 1998), activation of CB1 is required for the axonal growth response (Williams et al. 2003), the endocannabinoid system drives neural progenitor cell proliferation (Aguado et al. 2006), and cannabinoids actually promote neurogenesis (Berghuis et al. 2007).”