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Behavioral, psychophysiological and neurochemical changes underlying withdrawal from chronic treatment with the dissociative anesthetic ketamine


The lack of preclinical studies on the effects of ketamine, when administered continuously, as well as the possible emergence of withdrawal symptoms after the abrupt cessation of its use, are issues still little discussed in the literature. Studies in this line of research make it even more necessary, taking into account the dissemination of ketamine among young people who, as a rule, commonly use this drugjointly with other substances, particularly with stimulants of the central nervous system. Thisproject is intended to fill part of this deficiency by analyzing the effects of ketamine in experimental animals using a variety of experimental models and techniques, in which some of the neurochemical, pharmacological, electrophysiological and behavioral changes consequent to its acute and chronic use, as well as a possible withdrawal syndrome elicited by withdrawal, will be investigated. Initially, the experiments described below are intended to investigate the behavioral changes promoted by the chronic administration of ketamine, regarding its positive and negative reinforcing effects (the role on motivated behavior). Then, we go to analyze the chronic effects of ketamine on the glutamatergic, dopaminergic and serotonergic systems of the infralimbic cortex and nucleus accumbens shell, as well as on the expression of the unconditioned "anxiety-like" behavior and on the processing of auditory sensory information evoked in the midbrain tectum. Finally, we will conclude this study by analyzing the effects of chronic ketamine administration on the attentional processes modulated by the aforementioned regions, and on themodulation/expression of unconditioned and conditioned defensive responses. (AU)

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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)
PALIARIN, FRANCIELY; INCROCCI, ROBERTA MONTEIRO; NOBRE, MANOEL JORGE. Behavioral and Auditory Electrophysiological Rebound as a Compensatory Response to the Reinforcing Effects of Morphine. Neuroscience, v. 392, p. 66-76, . (14/23690-5)
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, . (17/18268-0, 14/23690-5)

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