Effects of intra-prelimbic prefrontal cortex injection of cannabidiol on anxiety-like behavior: Involvement of 5HT(1A) receptors and previous stressful experience

Author(s)

Fogaca, M. V. ^{[1, 2, 3]} ; Reis, F. M. C. V. ^{[3, 4]} ; Campos, A. C. ^{[5, 6, 7, 3]} ; Guimaraes, F. S. ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, INeC, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Sch Philosophy Sci & Letters Ribeirao Preto, Psychol Dept, BR-14049900 Ribeirao Preto, SP - Brazil

^[5] Univ Fed Minas Gerais, Sch Med, Belo Horizonte, MG - Brazil

^[6] Univ Fed Minas Gerais, Inst Biol Sci, Lab Immunopharmacol, Grp Neuroimmunol, Belo Horizonte, MG - Brazil

^[7] Univ Fed Minas Gerais, Sch Med, Infect Dis & Trop Med Program, Belo Horizonte, MG - Brazil

• Document type: Journal article
• Source: European Neuropsychopharmacology; v. 24, n. 3, p. 410-419, MAR 2014.
• Web of Science Citations: 48

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 5HT(1A) 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 5HT(1A) 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 5HT(1A) 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 5HT(1A) 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 5HT(1A)-mediated neurotransmission and previous stressful experience. (c) 2013 Elsevier B.V. and ECNP. All rights reserved. (AU)

• FAPESP's process: 12/17626-7 - Cellular and molecular mechanisms involved in the role of atypical neurotransmitters in neuropsychiatric disorders
• Grantee: Francisco Silveira Guimaraes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/50896-8 - Cannabidiol regulation of fear memory processing and associated brain function
• Grantee: Francisco Silveira Guimaraes
• Support Opportunities: Regular Research Grants