Chronic intracerebroventricular infusion of lipopolysaccharide: effects of ibuprofen treatment and behavioural and histopathological correlates

Twenty male Wistar rats were trained under an alternating-lever cyclic-ratio (ALCR) schedule of food reinforcement. When responding showed no trends, each subject was subcutaneously implanted with an Alzet osmotic mini-pump, connected to a chronic indwelling cannula extending into the lateral ventricle of the brain. The mini-pumps were primed to infuse 0.25 mu l lipopolysaccharide (LPS) (1.0 mu g/0.25ml) or 0.25 mu l artificial cerebrospinal fluid (aCSF) per hour and were implanted for 28 days. LIDS infusion produced behavioural deficits which chronic ibuprofen treatment (40 mg/kg every 12 h) alleviated. Infusion of LIDS induced R1282-positive amyloid deposits, and activation of microglia and astrocytes. lbuprofen treatment reduced the numbers of activated microglia, and withdrawal of ibuprofen resulted in an increase in activated microglia; however, ibuprofen treatment had no effect on numbers of activated astrocytes in the LPS-infused subjects.