Effects of intra-prelimbic prefrontal cortex injection of cannabidiol on anxiety-like behavior: Involvement of 5HT1A receptors and previous stressful experience

• Published in: European neuropsychopharmacology Vol. 24; no. 3; pp. 410 - 419
• Main Authors: Fogaça, M.V, Reis, F.M.C.V, Campos, A.C, Guimarães, F.S
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2014
• Subjects: 5HT1A receptors; Animals; Anti-Anxiety Agents - administration & dosage; Anti-Anxiety Agents - pharmacology; Anxiety; Anxiety - drug therapy; Anxiety - physiopathology; Cannabidiol; Cannabidiol - administration & dosage; Cannabidiol - pharmacology; Cannabis sativa; Conditioning (Psychology) - drug effects; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Exploratory Behavior - drug effects; Fear - drug effects; Glucocorticoids; Internal Medicine; Male; Maze Learning - drug effects; Metyrapone - pharmacology; Piperazines - pharmacology; Prefrontal cortex; Prefrontal Cortex - drug effects; Prefrontal Cortex - physiopathology; Psychiatry; Pyridines - pharmacology; Raphe Nuclei - drug effects; Raphe Nuclei - physiopathology; Rats, Wistar; Receptor, Serotonin, 5-HT1A - metabolism; Restraint, Physical; Serotonin 5-HT1 Receptor Antagonists - pharmacology; Stress; Stress, Psychological - physiopathology; Time Factors; Cannabidiol; Anxiety; Prefrontal cortex; Glucocorticoids; 5HT 1A receptors; Stress; 5HT1A receptors; 5HT(1A) receptors
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/j.euroneuro.2013.10.012

Abstract The prelimbic medial prefrontal cortex (PL) is an important encephalic structure involved in the expression of emotional states. In a previous study, intra-PL injection of cannabidiol (CBD), a major non-psychotomimetic cannabinoid present in the Cannabis sativa plant, reduced the expression of fear conditioning response. Although its mechanism remains unclear, CBD can facilitate 5HT1A receptor-mediated neurotransmission when injected into several brain structures. This study was aimed at verifying if intra-PL CBD could also induce anxiolytic-like effect in a conceptually distinct animal model, the elevated plus maze (EPM). We also verified if CBD effects in the EPM and contextual fear conditioning test (CFC) depend on 5HT1A receptors and previous stressful experience. CBD induced opposite effects in the CFC and EPM, being anxiolytic and anxiogenic, respectively. Both responses were prevented by WAY100,635, a 5HT1A receptor antagonist. In animals that had been previously (24 h) submitted to a stressful event (2 h-restraint) CBD caused an anxiolytic, rather than anxiogenic, effect in the EPM. This anxiolytic response was abolished by previous injection of metyrapone, a glucocorticoid synthesis blocker. Moreover, restraint stress increased 5HT1A receptors expression in the dorsal raphe nucleus, an effect that was attenuated by injection of metyrapone before the restraint procedure. Taken together, these results suggest that CBD modulation of anxiety in the PL depend on 5HT1A -mediated neurotransmission and previous stressful experience.