title: Escalating morphine exposures followed by withdrawal in feline immunodeficiency virus-infected cats: a model for HIV infection in chronic opiate abusers.
abstract: Opiate abuse is a risk factor for human immunodeficiency virus (HIV) infection. Because the direct effects of opiates on HIV infection are difficult to determine epidemiologically, animal models of lentivirus infection are relied upon to study the effects of opiates in the absence of confounding factors. Morphine, the predominant metabolite of heroin, is used in most experimental systems examining heroin abuse. In this study, morphine treatment of feline immunodeficiency virus (FIV)-infected cats modeled a typical pattern of escalating drug use interspersed with withdrawals. Plasma cortisol levels were measured for evidence of stress associated with morphine withdrawal. In the morphine-treated cats, cortisol levels peaked at time points corresponding to morphine withdrawal and returned to baseline levels during treatment and several weeks after the final withdrawal. Morphine-treated cats displayed clear behavioral and physical signs of opiate exposure and evidence of withdrawal when the drug was stopped. Morphine-exposed cats did not experience enhanced severity of FIV-related disease; in fact, morphine demonstrated a protective effect on FIV-associated changes in brainstem auditory evoked potentials. Our research suggests that opiate exposure is unlikely to adversely affect the progression of acute lentivirus infection and might be beneficial in controlling associated neurological disease.
authors.affiliation: Vaccine Research Institute of San Diego, 3030 Bunker Hill St., San Diego, CA 92109, USA.
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Barr
authors.forename: Salvador
authors.initials: S
authors.lastname: Huitron-Resendiz
authors.forename: Manuel
authors.initials: M
authors.lastname: Sanchez-Alavez
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Henriksen
authors.forename: Tom R
authors.initials: TR
authors.lastname: Phillips
mesh_terms: D000818:Animals; D002415:Cats; D002908:Chronic Disease; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D016089:Immunodeficiency Virus, Feline; D016180:Lentivirus Infections / Q000188:drug therapy* / Q000821:virology*; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009293:Opioid-Related Disorders / Q000150:complications*; D012720:Severity of Illness Index; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000209:etiology*; D013997:Time Factors; D014766:Viremia / Q000097:blood / Q000821:virology
chemical_list: D009020:Morphine; D006854:Hydrocortisone