Ameliorative effect of lithium chloride against d-galactose induced behavioral and memory impairment, oxidative stress and alteration in serotonin function in rats

Pharmacol Rep. 2019 Oct;71(5):909-916. doi: 10.1016/j.pharep.2019.04.022. Epub 2019 May 1.

Abstract

Background: Aging is a phenomenon that all living organisms surely face. d-galactose (D-gal) has been used to develop an aging model of brain. Lithium (Li) has been proposed to have neuroprotective properties in relation to several neurological disorders. The goal of the current studyis to evaluate the effect of Lithium Chloride (LiCl) on D-gal induced neurological disorders and oxidative stress.

Methods: Rats were treated with D-gal at a dose of 300 mg/ml/kg and various doses of LiCl (20, 40 and 80 mg/ml/kg) for 14 days. After that behavioral analysis (Elevated plus maze (EPM); Light dark box test (LDT); Morris water maze (MWM); Forced swim test (FST)) were performed. Animals were decapitated after behavioral tests and brain samples were collected for biochemical (malondialdehyde (MDA); superoxide dismutase (SOD); catalase (CAT); glutathione peroxidase (GPx); acetylcholiesterase (AChE)) and neurochemical analysis (5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA)).

Results: The results showed that administration of LiCl at all doses ameliorates D-gal induced, decreased time spent in the open arm and light box in EPM and LDT respectively, increased immobility in FST, increased latency escape in MWM, increased MDA levels, decreased antioxidant enzyme, increased AChE activity and decreased 5-HT metabolism.

Conclusions: In conclusion, the present study indicated that D-gal induced anxiety/depression like symptoms and memory impairment were ameliorated by LiCl (at all doses) possibly via its antioxidant effects and normalizing 5-HT function.

Keywords: Aging; Antioxidant enzyme; Lithium chloride; Oxidative stress; d-galactose.

MeSH terms

  • Aging / drug effects*
  • Aging / metabolism
  • Animals
  • Antioxidants / metabolism
  • Behavior, Animal / drug effects*
  • Brain / drug effects
  • Brain / metabolism
  • Galactose / toxicity
  • Lithium Chloride / pharmacology*
  • Male
  • Maze Learning / drug effects
  • Memory Disorders / prevention & control*
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism*

Substances

  • Antioxidants
  • Neuroprotective Agents
  • Serotonin
  • Lithium Chloride
  • Galactose