Acetylsalicylic acid reduces cigarette smoke withdrawal-induced anxiety in rats via modulating the expression of NFĸB, GLT-1, and xCT

Alaa M Hammad; Lujain F Alzaghari; Malek Alfaraj; Walid Al-Qerem; Wamidh H Talib; Fawaz Alasmari; Haneen Amawi; F Scott Hall

doi:10.3389/fphar.2022.1047236

Acetylsalicylic acid reduces cigarette smoke withdrawal-induced anxiety in rats via modulating the expression of NFĸB, GLT-1, and xCT

Front Pharmacol. 2023 Jan 9:13:1047236. doi: 10.3389/fphar.2022.1047236. eCollection 2022.

Authors

Alaa M Hammad¹, Lujain F Alzaghari¹, Malek Alfaraj¹, Walid Al-Qerem¹, Wamidh H Talib², Fawaz Alasmari³, Haneen Amawi⁴, F Scott Hall⁵

Affiliations

¹ Department of Pharmacy, College of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan.
² Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman, Jordan.
³ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
⁴ Department of Pharmacy Practice, Faculty of Pharmacy, Yarmouk University, Irbid, Jordan.
⁵ Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, United States.

Abstract

Background: Chronic exposure to cigarette smoke produces neuroinflammation and long-term changes in neurotransmitter systems, especially glutamatergic systems. Objective: We examined the effects of cigarette smoke on astroglial glutamate transporters as well as NF-κB expression in mesocorticolimbic brain regions, prefrontal cortex (PFC) and nucleus accumbens (NAc). The behavioral consequences of cigarette smoke exposure were assessed using open field (OF) and light/dark (LD) tests to assess withdrawal-induced anxiety-like behavior. Methods: Sprague-Dawley rats were randomly assigned to five experimental groups: a control group exposed only to standard room air, a cigarette smoke exposed group treated with saline vehicle, two cigarette smoke exposed groups treated with acetylsalicylic acid (ASA) (15 mg/kg and 30 mg/kg, respectively), and a group treated only with ASA (30 mg/kg). Cigarette smoke exposure was performed for 2 h/day, 5 days/week, for 31 days. Behavioral tests were conducted weekly, 24 h after cigarette smoke exposure, during acute withdrawal. At the end of week 4, rats were given either saline or ASA 45 min before cigarette exposure for 11 days. Results: Cigarette smoke increased withdrawal-induced anxiety, and 30 mg/kg ASA attenuated this effect. Cigarette smoke exposure increased the relative mRNA and protein expression of nuclear factor ĸB (NFĸB) in PFC and NAc, and ASA treatment reversed this effect. Also, cigarette smoke decreased the relative mRNA and protein expression of glutamate transporter1 (GLT-1) and the cystine-glutamate transporter (xCT) in the PFC and the NAc, while ASA treatment normalized their expression. Conclusion: Cigarette smoke caused neuroinflammation, alterations in glutamate transporter expression, and increased anxiety-like behavior, and these effects were attenuated by acetylsalicylic acid treatment.

Keywords: GLT-1; NFkB; XCT; acetylsalicylic acid; anxiety-like behavior.

Grants and funding

This work was supported by Al-Zaytoonah University of Jordan, grant number 26/12/2019–2020, and by the Researchers supporting project number (RSP 2022R235), King Saud University, Riyadh, Saudi Arabia.