Intracerebral HIV-1 glycoprotein 120 produces sickness behavior and pituitary-adrenal activation in rats: role of prostaglandins.
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 (i.c.v.) 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 i.c.v. 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.
Barak
Ohr
O
Department of Psychology, The Hebrew University of Jerusalem, Mount Scopus, Jerusalem 91905, Israel.
Weidenfeld
Joseph
J
Goshen
Inbal
I
Ben-Hur
Tamir
T
Taylor
Anna N
AN
Yirmiya
Raz
R
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001522:Behavior, Animal; D003345:Corticosterone / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D005334:Fever / Q000139:chemically induced / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012803:Sick Role
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015699:HIV Envelope Protein gp120; D000324:Adrenocorticotropic Hormone; D015232:Dinoprostone; D003345:Corticosterone; D007213:Indomethacin