title: The effect of gp120 on morphine's antinociceptive and neurophysiological actions.
abstract: Recently, we have shown that morphine's analgesic activity can be attenuated by chemokines, specifically CCL5 and CXCL12. Because the HIV-1 coat protein, glycoprotein 120 (gp120), binds to the same receptors as do CCL5 and CXCL12, experiments were designed to investigate the effect of gp120 in the brain on antinociception induced by morphine in the cold-water (-3°C) tail-flick (CWT) and hot-plate (+54°C) tests. In addition, mu-opioid-receptor-mediated effects in brain periaqueductal grey (PAG) slices were examined with whole-cell patch-clamp recordings. The results showed that (1) pretreatment with gp120 itself (10, 25, 50, 100 or 133 ng, PAG) had no nociceptive effect in the CWT; (2) pretreatment with gp120 (25 or 100 ng) dose-dependently reduced antinociception induced by subcutaneous (sc) injection of morphine (3 or 6 mg/kg) or PAG injection of morphine (100 ng) in the CWT; (3) a PAG injection of gp120 (133 ng), given 30 min before sc injection of morphine (6 mg/kg), similarly reduced morphine antinociception in the hot-plate test; (4) the inhibitory effect of gp120 on morphine-induced antinociception in the CWT was reversed by AMD3100, an antagonist of CXCR4; (5) pretreatment of slices with gp120 (200 pM) prevented morphine (10 μM)-induced hyperpolarization and reduction of input resistance in PAG neurons. Electrophysiology studies paralleled gp120-induced desensitization of a mu-opioid-receptor-mediated response in PAG neurons at the single-cell level. These studies are the first to demonstrate that the analgesic activity of morphine can be reduced by the presence of gp120 in the PAG and that pretreatment with AMD3100 is able to restore the analgesic effects of morphine.
authors.affiliation: Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, USA. chenyang@temple.edu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Chen
authors.forename: Lynn G
authors.initials: LG
authors.lastname: Kirby
authors.forename: Jonathan
authors.initials: J
authors.lastname: Palma
authors.forename: Khalid
authors.initials: K
authors.lastname: Benamar
authors.forename: Ellen B
authors.initials: EB
authors.lastname: Geller
authors.forename: Toby K
authors.initials: TK
authors.lastname: Eisenstein
authors.forename: Martin W
authors.initials: MW
authors.lastname: Adler
mesh_terms: D000698:Analgesia; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001596:Benzylamines; D003080:Cold Temperature; D000080027:Cyclams; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006358:Hot Temperature; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009020:Morphine / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects*; D058748:Pain Perception / Q000187:drug effects*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D001596:Benzylamines; D000080027:Cyclams; D015699:HIV Envelope Protein gp120; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D017450:Receptors, Opioid, mu; D009020:Morphine; C088327:plerixafor