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Effect of delta-9-tetrahydrocannabinol on behavioral despair and on pre- and postsynaptic serotonergic transmission.
Prog Neuropsychopharmacol Biol Psychiatry. 2012 Jul 02; 38(1):88-96.PN

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.

Authors+Show Affiliations

Neurobiological Psychiatry Unit, Dept. Psychiatry, McGill University, Montréal, Québec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

22386778

Citation

Bambico, Francis Rodriguez, et al. "Effect of Delta-9-tetrahydrocannabinol On Behavioral Despair and On Pre- and Postsynaptic Serotonergic Transmission." Progress in Neuro-psychopharmacology & Biological Psychiatry, vol. 38, no. 1, 2012, pp. 88-96.
Bambico FR, Hattan PR, Garant JP, et al. Effect of delta-9-tetrahydrocannabinol on behavioral despair and on pre- and postsynaptic serotonergic transmission. Prog Neuropsychopharmacol Biol Psychiatry. 2012;38(1):88-96.
Bambico, F. R., Hattan, P. R., Garant, J. P., & Gobbi, G. (2012). Effect of delta-9-tetrahydrocannabinol on behavioral despair and on pre- and postsynaptic serotonergic transmission. Progress in Neuro-psychopharmacology & Biological Psychiatry, 38(1), 88-96. https://doi.org/10.1016/j.pnpbp.2012.02.006
Bambico FR, et al. Effect of Delta-9-tetrahydrocannabinol On Behavioral Despair and On Pre- and Postsynaptic Serotonergic Transmission. Prog Neuropsychopharmacol Biol Psychiatry. 2012 Jul 2;38(1):88-96. PubMed PMID: 22386778.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of delta-9-tetrahydrocannabinol on behavioral despair and on pre- and postsynaptic serotonergic transmission. AU - Bambico,Francis Rodriguez, AU - Hattan,Patrick R, AU - Garant,Jean-Philippe, AU - Gobbi,Gabriella, Y1 - 2012/02/22/ PY - 2011/11/09/received PY - 2012/02/02/revised PY - 2012/02/13/accepted PY - 2012/3/6/entrez PY - 2012/3/6/pubmed PY - 2012/12/10/medline SP - 88 EP - 96 JF - Progress in neuro-psychopharmacology & biological psychiatry JO - Prog Neuropsychopharmacol Biol Psychiatry VL - 38 IS - 1 N2 - 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. SN - 1878-4216 UR - https://www.unboundmedicine.com/medline/citation/22386778/abstract/Effect_of_delta_9_tetrahydrocannabinol_on_behavioral_despair_and_on_presynaptic_and_postsynaptic_serotonergic_transmission_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-5846(12)00028-0 DB - PRIME DP - Unbound Medicine ER -