Involvement of 5-HT1A and 5-HT2C receptors of the dorsal hippocampus on the anxiolytic effect caused by antidepressant drugs

• Grant number: 12/20016-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): February 01, 2013
• Effective date (End): March 31, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Hélio Zangrossi Júnior
• Grantee: Ana Beatriz Sant Ana Do Nascimento
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 15/01544-0 - Neuronal circuits of passive and active fear behavior: focus on the role played by the medial prefrontal cortex in normal conditions and after antidepressant administration, BE.EP.DR

Abstract

The discovery of the anxiolytic properties of antidepressants (ADs) represented a great advance in the treatment of anxiety disorders. Clinical observations that selective serotonin re-uptake inhibitors are the first choice treatment for these pathologies highlighted the importance of serotonin in this process. Other evidence shows that the therapeutic effects of ADs develop only after chronic administration, suggesting that long-term neural adaptations are involved in the model of action of these drugs. It has been hypothesized that a progressive desensitization of 5-HT1A inhibitory autosomic receptors and/or alterations in postsynaptic 5-HT1A and 5-HT2 receptors sensitivity in forebrain structures, such as the hippocampus and amygdala, are involved in the delayed onset of ADs benefic effects. Studies using the elevated T-maze (ETM) revealed the involvement of 5-HT1A receptors on the basolateral nucleus of the amygdala (BLA) in the anxiolytic effect observed after chronic treatment with AD. They also evidenced the recruitment of 5-HT2C receptors of this same structure, in the anxiogenic effect observed after acute treatment with the same drugs. Compelling evidence shows the involvement of the dorsal hippocampus (DH) in the regulation anxiety-related defensive responses. It has been reported that in this brain area whereas stimulation of 5-HT1A receptors causes anxiogenic-like effect in the ETM, activation of 5-HT2C receptors causes the opposite effect. The aim of this study is to investigate the role of 5-HT1A and 5-HT2C of the DH on the anxiolytic and anxiogenic effects caused by ADs, as measured by different animal models of anxiety. To this end, both pharmacological (studies with antagonists) and genetic approaches (RNA interference) will be used.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANT'ANA, ANA BEATRIZ; VILELA-COSTA, HELOISA HELENA; VICENTE, MARIA ADRIELLE; HERNANDES, PALOMA MOLINA; CARNEIRO SPERA DE ANDRADE, TELMA GONCALVES; ZANGROSSI, JR., HELLO. Role of 5-HT2C receptors of the dorsal hippocampus in the modulation of anxiety- and panic-related defensive responses in rats. Neuropharmacology, v. 148, p. 311-319, APR 2019. (12/20016-6, 17/18437-7)