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

Behav Pharmacol. 2005 Nov;16(7):531-41. doi: 10.1097/01.fbp.0000179278.03868.96.

Abstract

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 microl lipopolysaccharide (LPS) (1.0 microg/0.25 ml) or 0.25 microl artificial cerebrospinal fluid (aCSF) per hour and were implanted for 28 days. LPS infusion produced behavioural deficits which chronic ibuprofen treatment (40 mg/kg every 12 h) alleviated. Infusion of LPS induced R 1282-positive amyloid deposits, and activation of microglia and astrocytes. Ibuprofen 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / metabolism
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antigens / metabolism
  • Astrocytes / pathology
  • Behavior, Animal / drug effects*
  • Brain / pathology*
  • Food
  • Glial Fibrillary Acidic Protein / metabolism
  • Ibuprofen / pharmacology*
  • Immunohistochemistry
  • Injections, Intraventricular
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / toxicity*
  • Male
  • Memory / drug effects
  • Microglia / pathology
  • Neurofibrillary Tangles / pathology
  • Rats
  • Rats, Wistar
  • Reinforcement Schedule
  • Reinforcement, Psychology

Substances

  • Alzheimer's disease antigen
  • Amyloid beta-Peptides
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antigens
  • Glial Fibrillary Acidic Protein
  • Lipopolysaccharides
  • Ibuprofen