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.
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Two studies have shown that the levels of these enzymes were decreased by LDX in neuropsychiatric disorder models.
“In this sense, two studies have shown that the levels of these enzymes were decreased by LDX in neuropsychiatric disorder models [225, 226].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [226]
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“Given the pharmacokinetic profile of LDX in rats (Pennick, 2010), we can estimate that the dose of LDX 10 mg/kg selected for the present research (based”
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“Bipolar disorder (BD) is a severe mental disorder, which is associated with elevated suicide rates (Dennehy et al., 2011) and substantialmedical and psychiatric comorbidity (McIntyre et al., 2012; Soreca et al., 2008).”
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“In this sense, two studies have shown that the levels of these enzymes were decreased by LDX in neuropsychiatric disorder models [225, 226].”
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- Authors
- Macêdo, D. S., de Lucena, D. F., Queiroz, A. I. G., Cordeiro, R. C., Araújo, M. M., Sousa, F. C., Vasconcelos, S. M., Hyphantis, T. N., Quevedo, J., McIntyre, R. S., & Carvalho, A. F.
- Affiliations
- Universidade Federal do Ceará (BR)
- University of Ioannina (GR)
- University Health Network (CA)
- ORCID
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 43
- Pages
- 230-237
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W1997383288
- Cited by
- 50
- References
- 6
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 6 · 2017: 6 · 2016: 5 · 2015: 5 · 2014: 4 · 2013: 4
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- lisdexamfetamine dimesylate, lithium, mania, animal model of mania, bipolar disorder, oxidative stress, hyperlocomotion, glutathione, lipid peroxidation, prefrontal cortex, hippocampus, striatum, amphetamine
- MeSH terms
- Lisdexamfetamine Dimesylate, Central Nervous System Stimulants, Animals, Behavior, Animal, Bipolar Disorder, Brain Chemistry, Dextroamphetamine, Dose-Response Relationship, Drug, Glutathione, Hippocampus, Lithium, Male, Motor Activity, Lipid Peroxidation, Lithium Carbonate, Neostriatum, Rats, Wistar, Thiobarbituric Acid Reactive Substances, Prefrontal Cortex, Oxidative Stress, Antimanic Agents, Rats
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