Effects of fluoxetine on 5-HT1A receptors located in different dorsal raphe subnuclei: an optogenetic and eletrophysiological approach

• Grant number: 15/11782-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): August 01, 2015
• Effective date (End): July 31, 2016
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Hélio Zangrossi Júnior
• Grantee: Heloísa Helena Vilela Costa
• Supervisor: Stefan Herlitze
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: Ruhr-Universität Bochum (RUB), Germany
• Associated to the scholarship: 13/05903-9 - Effect of administration of fluoxetine and imipramine on serotonergic neurotransmission in different subregions of the dorsal raphe nucleus and dorsal periaqueductal gray of rats exposed to model elevated T maze, BP.DR

Abstract

A wealth of evidence indicates that the dorsal raphe nucleus (DR) is a heterogeneous structure with different pattern of neuronal activation observed after expression of anxiety- and panic-related defensive responses. Antidepressant (AD) drugs are the first choice in treatment of anxiety disorders, and the delay for the therapeutic effect, have consistently been associated with changes in serotonergic neurotransmission within DR, mainly through alteration in the functioning of 5-HT1A receptors. It has been proposed that repeated treatment with AD is able to desensitize the 5-HT1A autoreceptors and serotonergic neurons regain their normal firing rate, which is required for these drug effects. Although, it has been reported differences on the pattern of neuronal activation and on the 5-HT1A receptor distribution among DR subnuclei, no study has yet addressed whether AD may impact the functioning of the DR in a regionally different way. The research group led by Professor Stefan Herlitze developed a new optogenetic approach that allows 5-HT1A receptor manipulation, specifically. Fusion of the native 5-HT1A to an opsin targets the light activated 5-HT1A receptor chimera, which could functionally and competitively substitute 5-HT1A signaling responses. By using this new optogenetic tool in animals treated with fluoxetine, we could investigate the profile of 5-HT1A receptor functionality on dorsal raphe subnuclei, which will be evaluated by electrophysiological recording. Additionally, we will use a transgenic mouse line, in which a Cre recombinase is exclusively expressed in serotonergic neurons, to express the 5-HT1A receptor chimera in serotonergic neurons only.