Intracerebral HIV-1 glycoprotein 120 produces sickness behavior and pituitary-adrenal activation in rats: Role of prostaglandins

Ohr Barak, Joseph Weidenfeld, Inbal Goshen, Tamir Ben-Hur, Anna N. Taylor, Raz Yirmiya*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

HIV infection is associated with profound neurobehavioral and neuroendocrine impairments. Previous studies demonstrated that HIV causes neuropathological alterations indirectly, via shedding of glycoprotein 120 (gp120) within the brain. To extend these findings, we examined the neurobehavioral and neuroendocrine effects of central administration of gp120, as well as the role of brain prostaglandins in mediating these effects. Intracerebroventricular (icv) injection of gp120 in rats produced a marked sickness behavior syndrome, consisting of reduced exploratory behavior, suppressed consumption of food and saccharin solution, and reduced body weight. Gp120 also induced a significant febrile response and increased serum levels of ACTH and corticosterone. Following icv gp120 administration, the ex vivo production of PGE2 by the hypothalamus, frontal cortex, and hippocampus was significantly elevated, and indomethacin, a prostaglandin synthesis inhibitor, attenuated this elevation. Pre-treatment with indomethacin reduced the fever and adrenocortical activation induced by gp120 administration, but not its behavioral effects. These findings indicate that gp120 may be responsible for some of the behavioral and endocrine abnormalities seen in HIV-infected patients. Prostaglandins are important mediators of the physiological, but not the behavioral effects of brain gp120.

Original languageAmerican English
Pages (from-to)720-735
Number of pages16
JournalBrain, Behavior, and Immunity
Volume16
Issue number6
DOIs
StatePublished - 2002

Bibliographical note

Funding Information:
The authors thank Edna Cohen, Nadav Mishaan, and Roee Canaan for their help in running the experiments. This work was supported by Grant 97-204 from the United-States– Israel Binational Science Foundation. R. Yirmiya is a member of the Eric Roland Center for Neurodegenerative Diseases at The Hebrew University of Jerusalem.

Keywords

  • Fever
  • Gp120
  • HIV
  • HPA axis
  • Indomethacin
  • Prostaglandin E (PGE)
  • Sickness behavior

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