Jonathan Palma1, Mary E Abood1, Mary F Barbe2, Khalid Benamar3. 1. Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA. 2. Department of Anatomy and Cell Biology, Philadelphia, PA, USA. 3. Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA. Electronic address: kbenamar@temple.edu.
Abstract
BACKGROUND: Recently we found that fever (part of HIV-related wasting) is induced by the action of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein (gp120) in the preoptic anterior hypothalamus (POAH). As the opioid system plays a role in the pathogenesis of HIV-1, in the present study we sought to examine the capacity of the opioid system to regulate the febrile response induced by gp120. METHODS: Stainless steel cannulas were stereotactically into the POAH, and a biotelemetry system was used to monitor the body temperature (Tb changes). We examined the in vivo effects of naloxone as well as highly opioid-selective receptor antagonists, on gp120-induced fever. RESULTS: Pretreatment with naloxone or the mu-opioid receptor-selective antagonist, cyclic d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP), significantly delayed the febrile response induced by gp120. In contrast, naltriben (NTB), a selective antagonist for the delta-2 opioid receptor, did not cause any effect on gp120-induced fever. CONCLUSION: These results (1) provide pharmacologic evidence of a functional in vivo interaction between the opioid system and this viral protein in the POAH and (2) show that mu-opioid receptors can regulate gp120-induced fever.
BACKGROUND: Recently we found that fever (part of HIV-related wasting) is induced by the action of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein (gp120) in the preoptic anterior hypothalamus (POAH). As the opioid system plays a role in the pathogenesis of HIV-1, in the present study we sought to examine the capacity of the opioid system to regulate the febrile response induced by gp120. METHODS:Stainless steel cannulas were stereotactically into the POAH, and a biotelemetry system was used to monitor the body temperature (Tb changes). We examined the in vivo effects of naloxone as well as highly opioid-selective receptor antagonists, on gp120-induced fever. RESULTS: Pretreatment with naloxone or the mu-opioid receptor-selective antagonist, cyclic d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP), significantly delayed the febrile response induced by gp120. In contrast, naltriben (NTB), a selective antagonist for the delta-2 opioid receptor, did not cause any effect on gp120-induced fever. CONCLUSION: These results (1) provide pharmacologic evidence of a functional in vivo interaction between the opioid system and this viral protein in the POAH and (2) show that mu-opioid receptors can regulate gp120-induced fever.
Authors: Imre Szabo; Xiao-Hong Chen; Li Xin; Martin W Adler; O M Z Howard; Joost J Oppenheim; Thomas J Rogers Journal: Proc Natl Acad Sci U S A Date: 2002-07-18 Impact factor: 11.205