Cortical changes induced by chronic administration of ketamine and its influence on emotional, locomotor and attentional aspects of rats tested at different stages of the estrous cycle

• Grant number: 14/09685-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2014
• End date: September 30, 2017
• Field of knowledge: Humanities - Psychology - Physiological Psychology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Manoel Jorge Nobre Do Espirito Santo
• Grantee: Renata Ferreira Sgobbi
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Ketamine, a noncompetitive NMDA receptor antagonist, has potent psychomimetic effects, being able to accentuate the psychotic state of schizophrenic patients. One of the brain areas affected by its use is the prefrontal cortex, as the performance on tasks dependent upon their activity is deeply influenced by the acute administration of ketamine. As in schizophrenia, these changes may be modulated by hormonal factors, and can be explained by the influence of female sex hormones such as estrogen, which have a very regulatory role in dopaminergic, serotonergic, glutamatergic and GABAergic systems; all of them affected by the acute and chronic effects of ketamine. Atencional disturbances are one of the symptoms present in psychoses, such as schizophrenia, and also in drug abuse. In preclinical studies, the use of prepulse inhibition (PPI) for analysis of this phenomenon made possible the identification of underlying neural systems and plays an important role in translational research, since IPP is a phenomenon that occurs in all mammals including rodents and humans and non-human primates. The IPP is heavily regulated by cortico-limbic circuits in rats, among which hippocampal afferents to the prefrontal cortex, which appear to regulate the conscious and direct inhibition of a motor response to an impulse. This becomes important as the lack of capacity for the controlled substance use underlies the changing in the relationship of the individual with the drug, turning its recreational use in contumacious intake. These brain areas have the ability to modulate multiple instances of behavior, including spatial orientation and temporal ordering, social and emotional behavior, associative learning, habituation and behavioral inhibition, among others. In this project we examine the effects of chronic administration and withdrawal of ketamine on locomotor, emotional, and attentional processes of female Wistar rats, tested at different stages of the estrous cycle, as well as the effects of pharmacological modulation of dopaminergic and glutamatergic systems of the medial prefrontal cortex on these variables. This first study will focus exclusively on the fronto -medial area of the prefrontal cortex, the well-known pre-limbic cortex (PrL). (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)

SGOBBI, RENATA FERREIRA; NOBRE, MANOEL JORGE. Differential effects of early exposure to alcohol on alcohol preference and blood alcohol levels in low- and high-anxious rats. Experimental Brain Research, v. 238, n. 12, p. 2753-2768, DEC 2020. (10/15157-4, 14/09685-9)