Doxycycline reversal of amphetamine-induced mania-like behavior is related to adjusting brain monoamine abnormalities and antioxidant effects in primary hippocampal neurons.

Autor: Chaves-Filho AJM; Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Universidade Federal do Ceará, Rua Cel. Nunes de Melo 1000, Fortaleza, CE, 60431-270, Brazil.; Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada., Soares MV; Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Universidade Federal do Ceará, Rua Cel. Nunes de Melo 1000, Fortaleza, CE, 60431-270, Brazil., Jucá PM; Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Universidade Federal do Ceará, Rua Cel. Nunes de Melo 1000, Fortaleza, CE, 60431-270, Brazil., Oliveira TQ; Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Universidade Federal do Ceará, Rua Cel. Nunes de Melo 1000, Fortaleza, CE, 60431-270, Brazil., Clemente DCDS; Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Universidade Federal do Ceará, Rua Cel. Nunes de Melo 1000, Fortaleza, CE, 60431-270, Brazil., Monteiro CEDS; Laboratory of Physiopharmacology Study of Gastrointestinal Tract, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil., Silva FGO; Laboratory of Physiopharmacology Study of Gastrointestinal Tract, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil., de Aquino PEA; Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Universidade Federal do Ceará, Rua Cel. Nunes de Melo 1000, Fortaleza, CE, 60431-270, Brazil., Macedo DS; Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Universidade Federal do Ceará, Rua Cel. Nunes de Melo 1000, Fortaleza, CE, 60431-270, Brazil. danielle.macedo@ufc.br.; National Institute for Translational Medicine (INCT-TM, CNPq), São Paulo, Brazil. danielle.macedo@ufc.br.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Aug; Vol. 397 (8), pp. 6017-6035. Date of Electronic Publication: 2024 Feb 22.
DOI: 10.1007/s00210-024-03009-7
Abstrakt: Mania is associated with disturbed dopaminergic transmission in frontotemporal regions. D-amphetamine (AMPH) causes increased extracellular DA levels, considered an acknowledged mania model in rodents. Doxycycline (DOXY) is a second-generation tetracycline with promising neuroprotective properties. Here, we tested the hypothesis that DOXY alone or combined with Lithium (Li) could reverse AMPH-induced mania-like behavioral alterations in mice by the modulation of monoamine levels in brain areas related to mood regulation, as well as cytoprotective and antioxidant effects in hippocampal neurons. Male Swiss mice received AMPH or saline intraperitoneal (IP) injections for 14 days. Between days 8-14, mice receive further IP doses of DOXY, Li, or their combination. For in vitro studies, we exposed hippocampal neurons to DOXY in the presence or absence of AMPH. DOXY alone or combined with Li reversed AMPH-induced risk-taking behavior and hyperlocomotion. DOXY also reversed AMPH-induced hippocampal and striatal hyperdopaminergia. In AMPH-exposed hippocampal neurons, DOXY alone and combined with Li presented cytoprotective and antioxidant effects, while DOXY+Li also increased the expression of phospho-Ser133-CREB. Our results add novel evidence for DOXY's ability to reverse mania-like features while revealing that antidopaminergic activity in some brain areas, such as the hippocampus and striatum, as well as hippocampal cytoprotective effects may account for this drug's antimanic action. This study provides additional rationale for designing clinical trials investigating its potential as a mood stabilizer agent.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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