Elevated anxiety, hypoactivity, memory deficits, decreases of brain serotonin and 5-HT-1A receptors expression in rats treated with omeprazole.

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Tytuł:: Elevated anxiety, hypoactivity, memory deficits, decreases of brain serotonin and 5-HT-1A receptors expression in rats treated with omeprazole.
Autorzy:: Ali SB; 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.
Mahmood K; 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.
Saeed R; 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.
Salman T; 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.
Choudhary MI; 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.
Haleem DJ; 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.
Źródło:: Toxicological research [Toxicol Res] 2020 Sep 17; Vol. 37 (2), pp. 237-248. Date of Electronic Publication: 2020 Sep 17 (Print Publication: 2021).
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Publication: 2020- : Singapore : Springer Singapore
Original Publication: Seoul : Korean Society of Toxicology
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Contributed Indexing:: Keywords: Anxiety-like behavior; Learning and memory; Motor activity; Omeprazole; Serotonin; Serotonin-1A receptors
Entry Date(s):: Date Created: 20210419 Latest Revision: 20220402
Update Code:: 20230925
PubMed Central ID:: PMC8007676
DOI:: 10.1007/s43188-020-00060-3
PMID:: 33868980
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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.
Competing Interests: Conflict of interestThe authors declare no conflict of interest.
(© Korean Society of Toxicology 2020.)

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