title: Effects of lithium on oxidative stress and behavioral alterations induced by lisdexamfetamine dimesylate: relevance as an animal model of mania.
abstract: Lisdexamfetamine dimesylate (LDX) is a prodrug that requires conversion to d-amphetamine (d-AMPH) for bioactivity. Treatment with d-AMPH induces hyperlocomotion and is regarded as a putative animal model of bipolar mania. Therefore, we sought to determine the behavioral and oxidative stress alterations induced by sub-chronic LDX administration as well as their reversal and prevention by lithium in rats. A significant increment in locomotor behavior was induced by LDX (10 and 30 mg/kg). To determine Li effects against LDX-induced alterations, in the reversal protocol rats received LDX (10 or 30 mg/kg) or saline for 14 days. Between days 8 and 14 animals received Li (47.5 mg/kg, i.p.) or saline. In the prevention paradigm, rats were pretreated with Li or saline prior to LDX administration. Glutathione (GSH) levels and lipid peroxidation was determined in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) of rats. Lithium prevented LDX-induced hyperlocomotion at the doses of 10 and 30 mg/kg, but only reversed LDX-induced hyperlocomotion at dose of 10mg/kg. In addition, both doses of LDX decreased GSH content (in ST and PFC), while Li was able to reverse and prevent these alterations mainly in the PFC. LDX (10 and 30 mg/kg) increased lipid peroxidation which was reversed and prevented by Li. In conclusion, LDX-induced hyperlocomotion along with associated increments in oxidative stress show promise as an alternative animal model of mania.
authors: Psychiatry Research Group, Federal University of Ceará, Faculty of Medicine, Fortaleza, Ceara, Brazil.
authors: Danielle S
authors: DS
authors: Macêdo
authors: David F
authors: DF
authors: de Lucena
authors: Ana Isabelle G
authors: AI
authors: Queiroz
authors: Rafaela C
authors: RC
authors: Cordeiro
authors: Maíra M
authors: MM
authors: Araújo
authors: Francisca Cléa
authors: FC
authors: Sousa
authors: Silvânia M
authors: SM
authors: Vasconcelos
authors: Thomas N
authors: TN
authors: Hyphantis
authors: João
authors: J
authors: Quevedo
authors: Roger S
authors: RS
authors: McIntyre
authors: André F
authors: AF
authors: Carvalho
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001714:Bipolar Disorder / Q000139:chemically induced* / Q000523:psychology*; D001923:Brain Chemistry / Q000187:drug effects; D000697:Central Nervous System Stimulants; D003913:Dextroamphetamine; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D000069478:Lisdexamfetamine Dimesylate; D008094:Lithium / Q000097:blood; D016651:Lithium Carbonate / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D018692:Antimanic Agents; D000697:Central Nervous System Stimulants; D017392:Thiobarbituric Acid Reactive Substances; D016651:Lithium Carbonate; D008094:Lithium; D005978:Glutathione; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine