title: Antidepressant Effects of Ketamine Are Not Related to ¹⁸F-FDG Metabolism or Tyrosine Hydroxylase Immunoreactivity in the Ventral Tegmental Area of Wistar Rats.
abstract: Major depressive disorder (MDD) is an important health problem that is often associated to stress. One of the main brain regions related to MDD is the ventral tegmental area (VTA), a dopaminergic center, part of the reward and motivation circuitry. Recent studies show that changes to VTA dopaminergic neurons are associated with depression and treatment. Ketamine has recently shown a fast, potent antidepressant effect in acute, sub-anesthetic doses. Thus, our aims were to elucidate if ketamine would be able to revert depression-like behaviors induced by a chronic unpredictable stress (CUS) protocol and if it could cause alterations to metabolism and tyrosine hydroxylase (TH)-immunoreactivity in VTA. For this, 48 Wistar rats were divided into four groups: control + saline (CTRL + SAL), control + ketamine (CTRL + KET), CUS + saline (CUS + SAL), CUS + ketamine (CUS + KET). The CUS groups underwent 28 days of CUS protocol. Saline or ketamine (10 mg/kg) was administered intraperitonially once on day 28. The behavior was assessed by the sucrose preference test, the open field test, and the forced swim test. Glucose brain metabolism was assessed and quantified with microPET. TH-immunoreactivity was assessed by estimating neuronal density and regional and cellular optical densities. A decrease in sucrose intake in the CUS groups and an increase in immobility was rapidly reverted by ketamine (p < 0.05). No difference was observed in the open field test. There was no alteration to VTA metabolism and TH-immunoreaction. These results suggest that the depressive-like behavior induced by CUS and the antidepressant effects of ketamine are unrelated to changes in neuronal metabolism or dopamine production in VTA.
authors.affiliation: Laboratório de Biologia Celular e Tecidual e Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Ciências Morfofisiológicas, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Avenida Ipiranga, 6681, Prédio 12, Sala 104, Porto Alegre, RS, CEP 90619-900, Brazil, pedropoa@gmail.com.
authors.forename: Pedro Porto Alegre
authors.initials: PP
authors.lastname: Baptista
authors.forename: Lisiani
authors.initials: L
authors.lastname: Saur
authors.forename: Pamela Bambrilla
authors.initials: PB
authors.lastname: Bagatini
authors.forename: Samuel
authors.initials: S
authors.lastname: Greggio
authors.forename: Gianina Teribele
authors.initials: GT
authors.lastname: Venturin
authors.forename: Sabrina Pereira
authors.initials: SP
authors.lastname: Vaz
authors.forename: Kelly Dos Reis
authors.initials: Kdos R
authors.lastname: Ferreira
authors.forename: Juliana Silva
authors.initials: JS
authors.lastname: Junqueira
authors.forename: Diogo Rizzato
authors.initials: DR
authors.lastname: Lara
authors.forename: Jaderson Costa
authors.initials: JC
authors.lastname: DaCosta
authors.forename: Cristina Maria Moriguchi
authors.initials: CM
authors.lastname: Jeckel
authors.forename: Régis Gemerasca
authors.initials: RG
authors.lastname: Mestriner
authors.forename: Léder Leal
authors.initials: LL
authors.lastname: Xavier
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005518:Food Preferences / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000150:complications / Q000523:psychology; D013550:Swimming / Q000523:psychology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000000981:diagnostic imaging* / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D007649:Ketamine; D014446:Tyrosine 3-Monooxygenase; D005947:Glucose