5-HT1A receptors are involved in the anxiolytic effect of Delta9-tetrahydrocannabinol and AM 404, the anandamide transport inhibitor, in Sprague-Dawley rats.
Daniela Braida, Valeria Limonta, Lorenzo Malabarba, Alessia Zani, Mariaelvina Sala
European Journal of Pharmacology January 26, 2007 DOI: 10.1016/j.ejphar.2006.10.038 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Sprague-Dawley rats |
| Interventions | Delta9-tetrahydrocannabinol (THC) WAY-100635 8-Hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT) |
| Dose | THC 0.075-0.75 mg/kg i.p.; AM 404 0.75-1.25 mg/kg i.p.; ineffective THC 0.015 mg/kg; ineffective AM 404 0.015 mg/kg; WAY-100635 300 microg/kg s.c.; 8-OH-DPAT 7.5 microg/kg i.p. |
| Measures | elevated plus maze test, activity cage |
| Topics | Cannabis Serotonin |
| Key findings | THC and the anandamide transporter inhibitor AM 404 each produced dose-dependent anxiolytic effects in the elevated plus maze that were blocked by the 5-HT1A antagonist WAY-100635, and ineffective doses of either drug combined with an ineffective dose of the 5-HT1A agonist 8-OH-DPAT produced synergistic anxiolysis. The authors suggest that cannabinoid anxiolytic effects are modulated by 5-HT1A receptors. |
Abstract
The mechanism mediating the effects of cannabinoids on anxiety-related responses appear to involve cannabinoid CB1 and non-CB1 receptors. However, other neurotransmitters may play a role in such effect. This study shows evidence of an interaction between endocannabinoid system and serotonin (5-HT), 1A receptor subtype on anxiety-like behavior in Sprague-Dawley rats. The exogenous cannabinoid agonist, Delta9-tetrahydrocannabinol (THC), and N-(4-hydroxyphenyl)-arachidonylamide, the anandamide transporter inhibitor (AM 404) were evaluated in the elevated plus maze test. THC (0.075-0.75 mg/kg i.p.), given 30 min and AM 404 (0.75-1.25 mg/kg i. p.), given 60 min before the test, exhibited a dose-response anxiolytic effect evaluated in terms of increase in the percentage of total entries and time spent in the open and decrease of total entries and time spent in the closed arms. The anxiolytic effect obtained with the maximal active dose of both THC (0.75 mg/kg) and AM 404 (1.25 mg/kg) was blocked by the 5-HT1A receptor antagonist, N-[2-[4-(2-methoxyphenyl) piperazin-1-yl]ethyl]-N-pyridin-2-yl-cyclohexanecarboxamide dihydro chloride (WAY-100635 (300 microg/kg, s.c.), given 30 min before THC or 15 min before AM 404. The combination of an ineffective dose of THC (0.015 mg/kg) or AM 404 (0.015 mg/kg) on anxiety-related responses with an ineffective dose of the 5HT(1A) receptor agonist, 8-Hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT) (7.5 microg/kg, i.p.), led to a synergistic effect. No interference with spontaneous motor activity, evaluated in an activity cage for 5 min, in rats given the drugs alone or in combination, was found. These data suggest that the anxiolytic effect produced by endo- and eso-cannabinoids is modulated by 5-HT1A receptors.
Comparable studies
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Citations in the library
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- Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Archives of General Psychiatry 2009
- Legal highs: staying on top of the flood of novel psychoactive substances Therapeutic Advances in Psychopharmacology January 26, 2015
- Endocannabinoid system and psychiatry: in search of a neurobiological basis for detrimental and potential therapeutic effects Frontiers in Behavioral Neuroscience 2011
- Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties Journal of Translational Medicine October 2, 2020
- Chronic Δ9-tetrahydrocannabinol treatment has dose-dependent effects on open field exploratory behavior and [3H] SR141716A receptor binding in the rat brain. Life Sciences August 15, 2023
and 8 more in the library
Cites 3
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