The present work was undertaken in order to investigate the effects of systemic lipopolysaccharide endotoxin administration (250 μg/kg) on spatial memory formation and oxidative stress in rats subjected to right-unilateral lesion of the dopaminergic neurons of the substantia nigra by means of 6- hydroxydopamine (6-OHDA) compared to normal and lipopolysaccharide alone treated rats.

Thirty male Wistar rats weighing 200 ± 50 at the start of the experiment were used. The substantia nigra was right-unilateral lesioned by stereotaxic microinjections of 8 micrograms (free base) 6-OHDA. The rats were pretreated 30 min before the 6-OHDA infusion with 25 mg/kg desipramine to protect noradrenergic projections. Sham-operated rats received only an injection of desipramine, followed by vehicle in the substantia nigra. Lipopolysaccharide (LPS from Escherichia coli serotype 0111:B4, Sigma) was dissolved in pyrogen-free 0.9% NaCl at the concentration of 250 μg/kg and intraperitonealy injected in normal and 6-OHDA-lesioned rats for a period of 7 continuous days. 7 days after continuous LPS administration we assessed memory formation by means of Y-maze and radial arm-maze task, and the endogenous antioxidants activity in rat temporal cortical area.

Systemic lipopolysaccharide administration significantly decreased spontaneous alternation in Y-maze task, working memory and reference memory in radial arm-maze task, suggesting impairment of both short-term memory and long term-memory, respectively. Furthermore, lipopolysaccharide administration significantly decreased activity of the biochemical markers of endogenous antioxidants in rat temporal cortical area.

Our results further validate that lipopolysaccharide may exacerbate the development of neurological dysfunctions associated with Parkinson's disease.