Preclinical toxicological study of prolonged exposure to ketamine as an antidepressant

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dc.contributor.authorZaccarelli-Magalhaes J.
dc.contributor.authorFukushima A.R.
dc.contributor.authorMoreira N.
dc.contributor.authorManes M.
dc.contributor.authorde Abreu G.R.
dc.contributor.authorRicci E.L.
dc.contributor.authorWaziry P.A.F.
dc.contributor.authorSpinosa H.S.
dc.date.accessioned2024-03-12T23:48:55Z
dc.date.available2024-03-12T23:48:55Z
dc.date.issued2020
dc.description.abstract© 2019, Maj Institute of Pharmacology Polish Academy of Sciences.Background: Depression is one of the most common mentally debilitating diseases in the world. Ketamine has been recently identified as a potential novel antidepressant. Further animal model evaluations of the use of ketamine as an antidepressant are necessary to determine safety parameters for clinical use. Therefore, the objective of this study was to perform toxicological tests of prolonged treatment using three different doses of ketamine in adult male rats. Methods: The animals were divided into four groups: three treated with 5, 10 or 20 mg/kg of ketamine and a control group treated with saline solution. Intraperitoneal route of treatment was administered daily for 3 weeks. Body weight, water and food intake were measured once a week, as well as evaluation of the functional observational battery, which includes methodic monitoring of motor activity, motor coordination, behavioral changes, and sensory/motor reflex responses. Upon completion of treatment period, all animals were euthanized by decapitation followed by immediate collection of samples, which included brain structures and blood for neurochemical, hematological and biochemical analyses. Results: Rats treated with the highest tested dosage (20 mg/kg) of ketamine had lower weight gain in the 1st and 2nd weeks of treatment and all experimental groups had measurable alterations in the serotoninergic system. Conclusions: Our data indicate that the alterations observed are minor and due to a predicted mechanism of action, which implies that ketamine is a promising drug for repurposing as an antidepressant.
dc.description.firstpage24
dc.description.issuenumber1
dc.description.lastpage35
dc.description.volume72
dc.identifier.doi10.1007/s43440-019-00014-z
dc.identifier.issn2299-5684
dc.identifier.urihttps://dspace.mackenzie.br/handle/10899/35032
dc.relation.ispartofPharmacological Reports
dc.rightsAcesso Restrito
dc.subject.otherlanguageAntidepressant
dc.subject.otherlanguageBiochemistry
dc.subject.otherlanguageKetamine
dc.subject.otherlanguageNeurochemistry
dc.subject.otherlanguageToxicological safety
dc.titlePreclinical toxicological study of prolonged exposure to ketamine as an antidepressant
dc.typeArtigo
local.scopus.citations2
local.scopus.eid2-s2.0-85078875209
local.scopus.subjectAnimals
local.scopus.subjectAntidepressive Agents
local.scopus.subjectBehavior, Animal
local.scopus.subjectDepression
local.scopus.subjectDisease Models, Animal
local.scopus.subjectDose-Response Relationship, Drug
local.scopus.subjectKetamine
local.scopus.subjectMale
local.scopus.subjectMotor Activity
local.scopus.subjectRats
local.scopus.subjectRats, Wistar
local.scopus.subjectToxicity Tests
local.scopus.updated2024-05-01
local.scopus.urlhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85078875209&origin=inward
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