Elevated Anxiety, Hypoactivity, Memory Deficits, Decreases of Brain Serotonin and 5-HT-1A Receptors Expression in Rats Treated with Omeprazole

Overview

Journal Toxicol Res

Specialty Toxicology

Date 2021 Apr 19

PMID 33868980

Citations 10

Authors

Sadia Basharat Ali

Khalid Mahmood

Raheel Saeed

Tabinda Salman

Muhammad Iqbal Choudhary

Darakhshan Jabeen Haleem

Affiliations

Soon will be listed here.

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 . 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.

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