Effects of alpha-lipoic acid in an animal model of mania induced by D-amphetamine.

Abstract

OBJECTIVES:

Oxidative stress and neurotrophic factors are involved in the pathophysiology of bipolar disorder (BD). Alpha-lipoic acid (ALA) is a naturally occurring compound with strong antioxidant properties. The present study investigated ALA effects in an amphetamine-induced model of mania.

METHODS:

In the reversal protocol, adult mice were first given d-amphetamine (AMPH) 2 mg/kg, intraperitoneally (i.p.) or saline for 14 days. Between days 8 and 14, the animals received ALA 50 or 100 mg/kg orally, lithium (Li) 47.5 mg/kg i.p., or saline. In the prevention paradigm, mice were pretreated with ALA, Li, or saline prior to AMPH. Locomotor activity was assessed in the open-field task. Superoxide dismutase (SOD) activity, reduced glutathione (GSH), and thiobarbituric acid-reactive substance (TBARS) levels were evaluated in the prefrontal cortex (PFC), hippocampus (HC), and striatum (ST). Brain-derived neurotrophic factor (BDNF) levels were measured in the HC.

RESULTS:

ALA and Li prevented and reversed the AMPH-induced increase in locomotor activity. PREVENTION MODEL: ALA and Li co-administration with AMPH prevented the decrease in SOD activity induced by AMPH in the HC and ST, respectively; ALA and Li prevented GSH alteration in the HC and TBARS formation in all brain areas studied. REVERSAL MODEL: ALA reversed the decrease in SOD activity in the ST. TBARS formation was reversed by ALA and Li in all brain areas. Furthermore, ALA reversed AMPH-induced decreases in BDNF and GSH in the HC.

CONCLUSIONS:

Our findings showed that ALA, similarly to Li, is effective in reversing and preventing AMPH-induced behavioral and neurochemical alterations, providing a rationale for the design of clinical trials investigating ALA's possible antimanic effect.

• Authors: Danielle S Macêdo, Camila D Medeiros, Rafaela C Cordeiro, Francisca Cléa Sousa, Júnia V Santos, Thomás A Morais, Thomas N Hyphantis, Roger S McIntyre, João Quevedo, André F Carvalho
• Journal: Bipolar disorders (Bipolar Disord) Vol. 14 Issue 7 Pg. 707-18 (Nov 2012) ISSN: 1399-5618 [Electronic] Denmark
• PMID: 22897629 (Publication Type: Journal Article)
• Copyright: © 2012 John Wiley and Sons A/S.

Chemical References

• Antimanic Agents
• Brain-Derived Neurotrophic Factor
• Central Nervous System Stimulants
• Thiobarbituric Acid Reactive Substances
• Malondialdehyde
• Thioctic Acid
• Superoxide Dismutase
• Lithium Chloride
• Glutathione
• Dextroamphetamine

Topics

• Animals
• Antimanic Agents (therapeutic use)
• Bipolar Disorder (blood, chemically induced, drug therapy)
• Brain (drug effects, metabolism, pathology)
• Brain-Derived Neurotrophic Factor (metabolism)
• Central Nervous System Stimulants (toxicity)
• Dextroamphetamine (toxicity)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Glutathione (metabolism)
• Lipid Peroxidation (drug effects)
• Lithium Chloride (blood, therapeutic use)
• Male
• Malondialdehyde (metabolism)
• Mice
• Motor Activity (drug effects)
• Superoxide Dismutase (metabolism)
• Thiobarbituric Acid Reactive Substances (metabolism)
• Thioctic Acid (therapeutic use)