An assay on the behavioral, neuropharmacological, and neurobiological changes induced by chronic ketamine in neural systems related to the auditory sensory processing.

• Grant number: 17/18268-0
• Support Opportunities: Regular Research Grants
• Duration: December 01, 2017 - November 30, 2019
• Field of knowledge: Humanities - Psychology - Physiological Psychology
• Principal Investigator: Manoel Jorge Nobre Do Espirito Santo
• Grantee: Manoel Jorge Nobre Do Espirito Santo
• Host Institution: Pró-Reitoria Acadêmica. Centro Universitário de Franca (UNI-FACEF). Franca , SP, Brazil

Abstract

Ketamine (KET) is a non-competitive NMDA-glutamate antagonist that shares the ability to modulate GABA and dopamine (DA) neurotransmission, as well. That is the reason for the stimulant, hypnotic and analgesic properties, and also for its harmful influence on mental state, as well. These unusual and disturbing effects, that limit the clinical use, poses KET as a recreational drug. Chronic KET administration changes normal encephalic activity and induces psychotic states. KET also changes field evoked-potentials including the auditory ones. The dissociative effects of KET are supposed to be due to the sensory overload consequent from a reduction exerted by the inhibitory top-down control on the mesencephalic bottom-up processes resulting in the induction of psychotic-like symptoms where cognitive impairment, emotional blunting, and auditory hallucinations are the core signs. Auditory hallucination is related to functional and structural abnormalities in several regions of this system, including the inferior colliculus (IC), thalamus (TL), primary auditory cortex (CA), and the medial prefrontal cortex (CPFm), with a significant contribution of NMDA, GABA, and dopamine receptors. In fact, the effects of KET on the sensory systems are powerful involving changes at the electrophysiological (PEAs) and cognitive domains, as revealed by studies using unconditioned or selective attention. The present study was sought to determine the influence of KET on the processing of auditory stimuli. Changes on this system, greatly contributing to the expression of anomalous behavior and accentuating the impairment of psychic functions. Besides, similarities among species enable to infer data obtained from translational models to the clinical domain. Although studies aimed to understand the pharmacological action of short- or long-term use of KET have been more focused on complex cognitive functions, such as those related to working memory and executive processing, this project is mainly directed to the study of the physiological and pharmacological consequences of chronic KET exposure, particularly in basic sensory processes. Our objective is to investigate the physiological changes induced by KET on the ascending auditory sensory information, and the effects of the pharmacological modulation of GLU, GABA, and DA receptors of cortical and key subcortical brain areas on the auditory processing. (AU)

Publicações científicas

(Referências obtidas automaticamente do Web of Science e do SciELO, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores)

INCROCCI, ROBERTA MONTEIRO; PALIARIN, FRANCIELY; NOBRE, MANOEL JORGE. Prelimbic NMDA receptors stimulation mimics the attenuating effects of clozapine on the auditory electrophysiological rebound induced by ketamine withdrawal. NeuroToxicology, v. 69, p. 1-10, DEC 2018. (17/18268-0, 14/23690-5)

SILVA-CARDOSO, GLEICE KELLI; NOBRE, MANOEL JORGE. Context-Specific Tolerance and Pharmacological Changes in the Infralimbic Cortex-Nucleus Accumbens Shell Pathway Evoked by Ketamine. Neurochemical Research, v. 46, n. 7, MAR 2021. (15/17568-5, 17/18268-0, 14/23690-5)