Elevated anxiety, hypoactivity, memory deficits, decreases of brain serotonin and 5-HT-1A receptors expression in rats t
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Toxicol Res. https://doi.org/10.1007/s43188-020-00060-3
Toxicological Research
ORIGINAL ARTICLE
Elevated anxiety, hypoactivity, memory deficits, decreases of brain serotonin and 5‑HT‑1A receptors expression in rats treated with omeprazole Sadia Basharat Ali1 · Khalid Mahmood1 · Raheel Saeed1 · Tabinda Salman1 · Muhammad Iqbal Choudhary1 · Darakhshan Jabeen Haleem1 Received: 10 March 2020 / Revised: 11 June 2020 / Accepted: 27 July 2020 © Korean Society of Toxicology 2020
Abstract Omeprazole (OM) is one of the most prescribed drugs worldwide for the treatment of hyperacidity and gastric reflux. However, concerns regarding its safety have emerged recently, and the drug is reported to enhance the risk for anxiety and cognitive deficits, particularly in elderly patients. The present study investigated these adverse effects, if any, in adult male rats. Associated changes in brain serotonin (5-hydroxytryptamine; 5-HT) and dopamine metabolism and the expression of 5-HT-1A receptors in the raphe and hippocampus were also determined. The drug was injected i.p. in doses of 10 and 20 mg/ kg for 15 days. Both doses of OM decreased motor activity in an open field and impaired learning and memory in the Morris water maze test. Anxiety monitored in an elevated plus maze test was enhanced in rats treated with 20 mg/kg OM only. The levels of 5-HT and its metabolite 5-hydroxyindoleacetic acid and of homovanillic acid, a metabolite of dopamine, determined by HPLC-EC, were decreased in the brain of OM treated rats. The expression of 5-HT-1A receptor, determined by qRT-PCR, was reduced markedly in the hippocampus and moderately in the raphe. Our results provide evidence that OM use can reduce raphe hippocampal serotonin neurotransmission to lead to anxiety/depression and cognitive impairment. There is a need for increased awareness and prescription guidelines for therapeutic use of OM and possibly also other proton pump inhibitors. Keywords Omeprazole · Motor activity · Anxiety-like behavior · Learning and memory · Serotonin · Serotonin-1A receptors
Introduction * Sadia Basharat Ali [email protected] * Darakhshan Jabeen Haleem [email protected] Khalid Mahmood [email protected] Raheel Saeed [email protected] Tabinda Salman [email protected] Muhammad Iqbal Choudhary [email protected] 1
Present Address: Neuroscience Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Omeprazole (OM) is one of the most widely prescribed proton pump inhibitors (PPIs) for treating gastric hyperacidity and reflux. It is a member of benzimidazole family and has been shown to block H+/K+-ATPase pump in the parietal cells of the stomach in the first 4 h after the administration [1]. In humans, the oral bioavailability of OM is about 40–50%, and elimination half-life from plasma is less than 1 h, and within 3–4 h it is entirely cleared from the plasma [2]. Its inhibitory action lasts up to
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