Behavioral and neurochemical effects of alpha lipoic acid associated with omega-3 in tardive dyskinesia induced by chronic haloperidol in rats

Can J Physiol Pharmacol. 2017 Jul;95(7):837-843. doi: 10.1139/cjpp-2016-0307. Epub 2017 Mar 22.

Abstract

Tardive dyskinesia (TD) is characterized by involuntary movements of the lower portion of the face being related to typical antipsychotic therapy. TD is associated with the oxidative imbalance in the basal ganglia. Lipoic acid (LA) and omega-3 (ω-3) are antioxidants acting as enzyme cofactors, regenerating antioxidant enzymes. This study aimed to investigate behavioral and neurochemical effects of supplementation with LA (100 mg/kg) and ω-3 (1 g/kg) in the treatment of TD induced by chronic use of haloperidol (HAL) (1 mg/kg) in rats. Wistar male rats were used, weighing between 180-200 g. The animals were treated chronically (31 days) with LA alone or associated with HAL or ω-3. Motor behavior was assessed by open-field test, the catalepsy test, and evaluation of orofacial dyskinesia. Oxidative stress was accessed by determination of lipid peroxidation and concentration of nitrite. LA and ω-3 alone or associated caused an improvement in motor performance by increasing locomotor activity in the open-field test and decreased the permanence time on the bar in the catalepsy test and decreased the orofacial dyskinesia. LA and ω-3 showed antioxidant effects, decreasing lipid peroxidation and nitrite levels. Thus, the use of LA associated with ω-3 reduced the extrapyramidal effects produced by chronic use of HAL.

Keywords: acide lipoïque; dyskinésie tardive; haloperidol; halopéridol; lipoic acid; omega-3; oméga 3; oxidative stress; stress oxydatif; tardive dyskinesia.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Drug Interactions
  • Fatty Acids, Omega-3 / pharmacology*
  • Fatty Acids, Omega-3 / therapeutic use
  • Haloperidol / adverse effects*
  • Lipid Peroxidation / drug effects
  • Male
  • Neurochemistry
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Tardive Dyskinesia / chemically induced
  • Tardive Dyskinesia / drug therapy*
  • Tardive Dyskinesia / metabolism*
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Thioctic Acid / pharmacology*
  • Thioctic Acid / therapeutic use

Substances

  • Fatty Acids, Omega-3
  • Thiobarbituric Acid Reactive Substances
  • Thioctic Acid
  • Haloperidol