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Involvement of D2 dopaminergic receptors in the expression and extinction of conditioned fear in females at different stages of the estrous cycle

Grant number: 19/20274-4
Support type:Scholarships in Brazil - Master
Effective date (Start): December 01, 2019
Effective date (End): November 30, 2021
Field of knowledge:Humanities - Psychology - Physiological Psychology
Principal Investigator:Amanda Ribeiro de Oliveira
Grantee:Camila de Oliveira Alves
Home Institution: Centro de Educação e Ciências Humanas (CECH). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Dopamine is a neurotransmitter that has been increasingly related to fear/anxiety states. Studies have shown that exposure to aversive conditioned stimuli leads to increased dopamine release in some structures, such as the amygdala and the nucleus accumbens. Such studies were mostly performed on males. Potential gender differences, taking into account, for example, the fact that the female brain operates in an environment of chemical changes caused by the cyclic production of sex hormones, needs further investigation. In this sense, we aim to evaluate the effects of sulpiride (a D2 dopaminergic receptor antagonist) on the expression and extinction of conditioned fear in females, broadening the characterization of the involvement of dopaminergic neurotransmission in conditioned fear and evaluating the influence of different phases of the estrous cycle. We will use 24 male and 120 female Wistar rats, weighing approximately 280 g. In Experiment 1, we will evaluate the efficacy of the contextual aversive conditioning protocol in the acquisition, expression and extinction of the conditioned freezing response in females (proestrus/estrus and metestrus/diestrus) compared to males rats. To do so, the animals will go through the training stage, in which there will be the presentation of footshocks. After 24 and 48 h, the animals will be submitted to the test and retest sessions, without presenting the footshocks, in the same context or in a different context from the training session, to evaluate the expression and extinction of the freezing response. In Experiment 2, we will evaluate the effects of sulpiride (20 and 40 mg/kg) on the expression and extinction of conditioned fear in females (proestrus/estrus and metestrus/diestrus). To this end, females will first undergo training in the contextual aversive conditioning protocol. After 24 h, sulpiride (20 or 40 mg/kg) or vehicle will be administered and then the female rats will be tested in the same context. After another 24 h, the animals will be retested, also in the same context. Potential motor effects will be evaluated with catalepsy and open field tests. (AU)