Fear extinction in an obsessive-compulsive disorder animal model: influence of sex differences and estrous cycle

• Grant number: 15/20487-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: January 01, 2016
• End date: December 28, 2016
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Marcus Lira Brandão
• Grantee: Adriano Edgar Reimer
• Supervisor: Mohammed Milad
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Massachusetts General Hospital, United States

Abstract

Obsessive-compulsive disorder (OCD) is a severe, chronic neurological condition that affects 2-3% of the population. Clinical studies and animal models have confirmed the importance of the serotonergic (5-HT) system in the neurobiology and treatment of OCD. In this context, the 5-HT agonist mCPP exacerbates symptoms in untreated OCD patients and, in rodents, it produces anxiety-like responses, repetitive behaviors and activates brain regions that correspond to aberrant regions of OCD patients. Although there is sufcient evidence indicating that 5-HT system is involved in OCD, the majority of animal studies have been conducted exclusively in male subjects, ignoring the inuence of sex and gonadal hormones. Given the prevalence of OCD in women, the exacerbation of OCD that seems to be related to reproductive events and the fact that sex hormones have been shown to interact with 5-HT system, it is plausible to picture an interplay between gonadal steroids and serotonergic system in OCD pathophysiology. Gonadal hormones also seem to influence the extinction of conditioned fear. This inability to appropriately inhibit fear is a central underlying feature of several anxiety disorders, among them OCD. Using mCPP to induce OCD symptoms, this study will investigate the potential sex differences and influence of estrous cycle and gonadal hormones in fear extinction learning/retention of rats. The experiments will not only broaden our knowledge about OCD pathophysiology, but may provide novel strategies for treatment based on gender. (AU)

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)

DE OLIVEIRA, AMANDA R.; REIMER, ADRIANO E.; REIS, FERNANDO M. C. V.; BRANDAO, MARCUS L.. Dopamine D-2-like receptors modulate freezing response, but not the activation of HPA axis, during the expression of conditioned fear. Experimental Brain Research, v. 235, n. 2, p. 429-436, FEB 2017. (16/04620-1, 15/20487-7)

REIMER, ADRIANO EDGAR; DE OLIVEIRA, AMANDA RIBEIRO; DINIZ, JULIANA BELO; HOEXTER, MARCELO QUEIROZ; MIGUEL, EURIPEDES CONSTANTINO; MILAD, MOHAMMED RAGIB; BRANDAO, MARCUS LIRA. Fear extinction in an obsessive-compulsive disorder animal model: Influence of sex and estrous cycle. Neuropharmacology, v. 131, p. 104-115, MAR 15 2018. (15/20487-7, 11/21357-9)