1 August 2019 | Volume 10 | Article 547 ORIGINAL RESEARCH doi: 10.3389/fpsyt.2019.00547 published: 05 August 2019 Frontiers in Psychiatry | www.frontiersin.org Edited by: Luca Steardo, Sapienza University of Rome, Italy Reviewed by: Anna Brancato, University of Palermo, Italy Maria Asuncion Aguilar, University of Valencia, Spain *Correspondence: Danielle S. Macedo danielle.macedo@ufc.br; daniellesilmacedo@gmail.com Specialty section: This article was submitted to Psychopharmacology, a section of the journal Frontiers in Psychiatry Received: 08 April 2019 Accepted: 15 July 2019 Published: 05 August 2019 Citation: Lima CNdC, da Silva FER, Chaves Filho AJM, Queiroz AIdG, Okamura AMNC, Fries GR, Quevedo J, de Sousa FCF, Vasconcelos SMM, de Lucena DF, Fonteles MMdF and Macedo DS (2019) High Exploratory Phenotype Rats Exposed to Environmental Stressors Present Memory Defcits Accompanied by Immune- Infammatory/Oxidative Alterations: Relevance to the Relationship Between Temperament and Mood Disorders. Front. Psychiatry 10:547. doi: 10.3389/fpsyt.2019.00547 High Exploratory Phenotype Rats Exposed to Environmental Stressors Present Memory Deficits Accompanied by Immune- Inflammatory/Oxidative Alterations: Relevance to the Relationship Between Temperament and Mood Disorders Camila Nayane de Carvalho Lima 1,2 , Francisco Eliclécio Rodrigues da Silva 1 , Adriano José Maia Chaves Filho 1 , Ana Isabelle de Gois Queiroz 1 , Adriana Mary Nunes Costa Okamura 1 , Gabriel Rodrigo Fries 2 , João Quevedo 2 , Francisca Cléa F. de Sousa 1 , Silvania Maria Mendes Vasconcelos 1 , David F. de Lucena 1 , Marta Maria de França Fonteles 1 and Danielle S. Macedo 1,4 * 1 Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Universidade Federal do Ceara, Fortaleza, Brazil, 2 Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, United States, 3 Department of Pharmacy, Faculty of Farmacy, Dentistry and Nursing, Universidade Federal do Ceara, Fortaleza, Brazil, 4 National Institute for Translational Medicine (INCT-TM, CNPq), Neurosciences and Behavior Department, Faculdade de Medicina de Ribeirão Preto (FMRP), Ribeirão Preto, Brazil Low-exploratory (LE) and high-exploratory (HE) rodents mimic human depressive and hyperthymic temperaments, respectively. Mood disorders (MD) may be developed by the exposure of these temperaments to environmental stress (ES). Psychiatric symptoms severity in MD patients is related to the magnitude of memory impairment. Thus, we aimed at studying the consequences of the exposure of LE and HE male Wistar rats, during periadolescence, to a combination of ES, namely, paradoxical sleep deprivation (PSD) and unpredictable stress (US), on anxiety-related behavior in the plus maze test, working (WM) and declarative memory (DM) performance. We also evaluated hippocampal immune-infammatory/oxidative, as consequences of ES, and prevention of ES-induced alterations by the mood-stabilizing drugs, lithium and valproate. Medium exploratory (ME) control rats were used for comparisons with HE- and LE-control rats. We observed that HE-controls presented increased anxiolytic behavior that was signifcantly increased by ES exposure, whereas LE-controls presented increased anxiety-like behavior relative to ME-controls. Lithium and valproate prevented anxiolytic alterations in HE+ES rats. HE+ES- and LE+ES-rats presented WM and DM defcits. Valproate and lithium prevented WM defcits in LE-PSD+US rats. Lithium prevented DM impairment in HE+ES-rats. Hippocampal levels of reduced glutathione (GSH) increased four-fold in HE+ES-rats,