Abstract

Preclinical and clinical studies suggest that direct and indirect cannabinoid agonists, including enhancers of endocannabinoids, engender stress-relieving, anxiolytic and antidepressant effects, mediated by central CB(1) receptors (CB(1)Rs). The effect of the main pharmacologically active principle in cannabis, (-)-trans-Δ(9)-tetrahydrocannabinol (delta-9-THC), on depressive behavior and on the serotonin (5-HT) system, which is implicated in the mechanism of action of antidepressants, has not been extensively clarified. Here, we showed that repeated (5 days), but not single (acute) intraperitoneal (ip) treatment with delta-9-THC (1mg/kg) exerts antidepressant-like properties in the rat forced swim test (FST). This effect was CB(1)R-dependent because it was blocked by the CB(1)R antagonist rimonabant (1mg/kg, ip). Using in vivo electrophysiology, we demonstrated that delta-9-THC modulated dorsal raphe (DR) 5-HT neuronal activity through a CB(1)R-dependent mechanism. Acute intravenous delta-9-THC administration (0.1-1.5mg/kg) elicited a complex response profile, producing excitatory, inhibitory and inert responses of 5-HT neurons. Only excitatory responses were blocked by rimonabant. Finally, repeated but not single delta-9-THC administration (1mg/kg, ip) enhanced tonic 5-HT(1A) receptor activity in the hippocampus, a postsynaptic event commonly elicited by standard antidepressants. These results suggest that delta-9-THC, like other CB(1)R agonists and endocannabinoid enhancers, may possess antidepressant properties at low doses, and could modulate 5-HT transmission in the DR and hippocampus as standard antidepressants such as selective serotonin reuptake inhibitors.

Links

Publisher Full Text

Authors

Bambico FR, Hattan PR, Garant JP, Gobbi G

Institution

Neurobiological Psychiatry Unit, Dept. Psychiatry, McGill University, Montréal, Québec, Canada.

Source

Progress in neuro-psychopharmacology & biological psychiatry 38:1 2012 Jul 2 pg 88-96

MeSH

Adaptation, Psychological
Animals
Behavior, Animal
Hippocampus
Male
Neurons
Rats
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT1A
Serotonergic Neurons
Synaptic Transmission
Tetrahydrocannabinol

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22386778