Female rats express heroin-induced and -conditioned suppression of peripheral nitric oxide production in response to endotoxin challenge

• Published in: Brain, behavior, and immunity Vol. 91; pp. 315 - 323
• Main Authors: Paniccia, Jacqueline E., Weckstein, Taylor N., Lebonville, Christina L., Lysle, Donald T.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.01.2021
• Subjects: Animals; Conditioning, Classical; Endotoxins; Female; Heroin; Heroin conditioning; Immune; Immune conditioning; Lipopolysaccharides; LPS; Male; Nitric Oxide; Nitric Oxide Synthase Type II; Opioid; Rats; Rats, Inbred Lew; Heroin conditioning; Immune; Opioid; Female; Heroin; LPS; Immune conditioning
• ISSN: 0889-1591; 1090-2139; 1090-2139
• DOI: 10.1016/j.bbi.2020.10.009

•Heroin attenuates typical induction of the peripheral immune response in male rats.•Heroin similarly suppresses endotoxin-induced peripheral nitric oxide in females.•Females express context-heroin conditioned suppression of nitric oxide production. Opioids and opioid-conditioned stimuli (CS) negatively alter host immunity, impairing the response to pathogens during opioid use and following drug cessation. Using male rats, our laboratory has determined that heroin or heroin-CS exposure preceding a lipopolysaccharide (LPS) challenge markedly suppresses normal induction of peripheral pro-inflammatory biomarkers. Presently, it is unknown if these heroin-induced and -conditioned effects extend to the female immune response. To begin this venture, the current study tested the direct effects of heroin and heroin-CS on LPS-induced peripheral nitric oxide (NO) production in female rats. We focused investigations on peripheral NO as it is a critical pro-inflammatory molecule necessary for pathogen resistance. In Experiment 1, male and female Lewis rats were administered 0 (Saline), 1, or 3 mg/kg heroin subcutaneously (s.c). Sixty minutes later, animals were injected with LPS (1 mg/kg, s.c.). Spleen and plasma samples were collected 6 h later to examine NO production through inducible NO synthase (iNOS) expression and nitrate/nitrite concentration, respectively. In Experiment 2, female Lewis rats underwent five, 60-minute context conditioning sessions with heroin (1 mg/kg, s.c.) or saline. On test day, CS-exposed and control (home cage) animals were injected with LPS (1 mg/kg, s.c.). Tissue was collected 6 h later to examine splenic iNOS expression and plasma nitrate/nitrite concentration. Both heroin administration alone and exposure to heroin-CS suppressed LPS-induced indices of NO production in spleen and plasma. Our results are the first to indicate that, similar to males, female rats express heroin-induced and -conditioned immunomodulation to a LPS challenge.