Omeprazole affects the expression of serotonin-1A in the brain regions and alleviates anxiety in rat model of immobilization-induced stress.

Omeprazole, a drug of choice for the management of gastric hyperacidity, influences serotonergic neurotransmission in brain regions and its long-term use is known to cause stress-related behavioral deficits including anxiety. Aim of the current study was to explore the effects of omeprazole treatment on immobilization-induced anxiety in rats, specifically on the role of serotonin (5-HT). In view of the role of serotonin-1A (5-HT1A) autoreceptor in the availability of 5-HT in brain regions, mRNA expression of this autoreceptor was performed in raphe nuclei. Similarly, because of the role of hippocampal 5-HT neurotransmission in anxiety-like disorders, expression of the 5-HT1A heteroreceptors was determined in this region. We found that the treatment with omeprazole reduces anxiety-like behavior in rats, increases the expression of 5-HT1A autoreceptor in the raphe and decreases the hippocampal expression of 5-HT1A heteroreceptor. This suggests a role of 5-HT1A receptor types in omeprazole-induced behavioral changes. It also indicates a potential role of omeprazole in the management of serotonergic disorders.

Behavioral, Hormonal, and Serotonergic Responses to Different Restricted Feeding Schedules in Rats.

To determine the effect of long-term restricted feeding schedules on behavior, serotonergic responses, and neuro-endocrine functions, metabolism of serotonin (5-HT) in the striatum, expression of serotonin-1A (5-HT1A) auto-receptor in the raphe nuclei and circulating levels of leptin and corticosterone were determined in female Wistar rats kept on excessive food restriction schedule. Due to a role of dietary deficiency of tryptophan (Trp) in influencing serotonergic neurotransmission, circulating levels of Trp were also determined. Estimations were done in 2 different restricted feeding models: time-restricted feeding (TRF) and diet restricted (DR). TRF animals were given access to food ad libitum only for 2 hours/day. The DR animals were given a small calculated amount of food each day. We found that chronic food restriction for 5 weeks cause a significant decrease in the body weight and produced hyperactivity in both, TRF and DR animals. Levels of Trp were declined in circulation and in the striatum. Similarly, the levels of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were decreased in the striatum. Also, the expression of 5-HT1A auto-receptor was declined in the raphe nuclei. These changes in 5-HT metabolism and 5-HT1A auto-receptor expression were more profound in DR animals as compare to TRF animals. Similarly, hypoleptinemia and increased corticosterone found in both models was higher in DR animals. Effect of dietary deficiency of Trp in the modulation of striatal 5-HT metabolism and its consequences on circulating leptin and corticosterone are discussed.

Prevention of diet restriction induced hyperactivity but not body-weight reduction in rats co-treated with tryptophan: relationship with striatal serotonin and dopamine metabolism and serotonin-1A auto-receptor expression.

Anorexia Nervosa (AN) is an eating and behavioral disorder characterized with anxiety/depression, hyperactivity, behavioral impulsivity and psychosis. Most of the associated symptoms are related to the deficiency of serotonin (5-hydroxytryptamine: 5-HT) stores. A deficiency of 5-HT can modulate dopamine neurotransmission in the striatum to elicit hyperactivity and psychosis in AN patients. Also, the release and availability of 5-HT are modulated by serotonin-1A (5-HT1A) auto-receptor. The present study investigates the role of striatal metabolism of 5-HT and dopamine in precipitating hyperactivity in the rat model of diet restriction (DR) induced AN. The role of tryptophan (Trp) in influencing the 5-HT metabolism and the mRNA expression of 5-HT1A auto-receptor is also investigated. We find that long-term DR for 38 days reduces body-weight in rats and produces hyperactivity, similar to AN. This hyperactivity is characterized by declined striatal metabolism of both, dopamine and 5-HT. The mRNA expression of 5-HT1A auto-receptor in the raphe nuclei is also decreased. Trp co-treatment improves these deficiencies in monoamine metabolism and alleviates hyperactivity. Interestingly, DR-induced changes in body-weights are not effected by Trp co-treatment. The study suggests that the striatal metabolism of 5-HT and dopamine and mRNA expression of 5-HT1A auto-receptor has an important role in the pathogenesis of AN. The finding suggests that co-use of Trp can prevent precipitation of AN by normalizing 5-HT metabolism.

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

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.