title: Anxiety-like behavior of mice produced by conditional central expression of the HIV-1 regulatory protein, Tat.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV) infection is associated with substantial increases in generalized anxiety. The HIV regulatory protein, transactivator of transcription (Tat), has been implicated in the neuropathogenesis related to HIV-1 infection. However, direct examination of the effect of Tat on behavioral measures of anxiety has not been demonstrated.
  
  
  OBJECTIVE
  To identify whether expression of the Tat1-86 protein exerts dose-dependent and persistent anxiety-like effects in a whole animal model, the GT-tg bigenic mouse.
  
  
  METHODS
  GT-tg mice and C57BL/6J controls were administered doxycycline in a dose- (0, 50, 100, or 125 mg/kg, i.p., for 7 days) or duration- (100 mg/kg, i.p., for 0, 1, 3, 5, or 14 days) dependent manner to induce Tat1-86 in brain. Mice were assessed for anxiety-like behavior in an open field, social interaction, or marble burying task 0, 7, and/or 14 days later. Central expression of Tat1-86 protein was verified with Western blot analyses.
  
  
  RESULTS
  Doxycycline produced no effects on C57BL/6J controls that lacked the Tat1-86 transgene. Among GT-tg mice, doxycycline (100 mg/kg for 3, 5, or 7 days) significantly increased anxiety-like behavior in all tasks, commensurate with enhanced Western blot labeling of Tat1-86 protein in brain, displaying optimal effects with the 7-day regimen. Greater exposure to doxycycline (either 125 mg/kg for 7 days or 100 mg/kg for 14 days) impaired locomotor behavior; whereas lower dosing (below 100 mg/kg) produced only transient increases in anxiety-like behavior.
  
  
  CONCLUSIONS
  Expression of HIV-1-Tat1-86 in GT-tg mouse brain produces exposure-dependent, persistent increases in anxiety-like behavior.
authors.affiliation: Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port Saint Lucie, FL, 34987, USA.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Paris
authors.forename: Harminder D
authors.initials: HD
authors.lastname: Singh
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Ganno
authors.forename: Pauline
authors.initials: P
authors.lastname: Jackson
authors.forename: Jay P
authors.initials: JP
authors.lastname: McLaughlin
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000139:chemically induced / Q000503:physiopathology*; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009483:Neuropsychological Tests; D011619:Psychotropic Drugs / Q000494:pharmacology; D013997:Time Factors; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D011619:Psychotropic Drugs; D054322:tat Gene Products, Human Immunodeficiency Virus; D004318:Doxycycline