We studied the antidepressant-like effect of paroxetine in strains of mice carrying different isoforms of tryptophan hydroxylase-2 (TPH-2), the enzyme responsible for the synthesis of brain serotonin (5-HT). The effect of paroxetine alone and in combination with pharmacological treatments enhancing or lowering 5-HT synthesis or melatonin was assessed in the forced swimming test in mice carrying allelic variants of TPH-2 (1473C in C57BL/6 and 1473G in DBA/2 and BALB/c). Changes in brain 5-hydroxytryptophan (5-HTP) accumulation and melatonin levels were measured by high-performance liquid chromatography. Paroxetine (2.5 and 5 mg/kg) reduced immobility time in C57BL/6J and C57BL/6N mice but had no such effect in DBA/2J, DBA/2N and BALB/c mice, even at 10 mg/kg. Enhancing 5-HT synthesis with tryptophan reinstated the antidepressant-like effect of paroxetine in DBA/2J, DBA/2N and BALB/c mice whereas inhibition of 5-HT synthesis prevented the effect of paroxetine in C57BL/6N mice. The response to paroxetine was not associated with changes in locomotor activity, brain melatonin or brain levels of the drug measured at the end of the behavioral test. These results support the importance of 5-HT synthesis in the response to SSRIs and suggest that melatonin does not contribute to the ability of tryptophan to rescue the antidepressant-like effect of paroxetine.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejphar.2008.07.031 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Polycystic Ovary Syndrome and Eating Disorders-A Literature Review.
J Clin Med
December 2024
Clinical Department of Gynecologic Surgery and Oncology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland.
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects women of reproductive age and is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. PCOS is often associated with hormonal imbalances, metabolic dysfunction and comorbid psychiatric disorders, including eating disorders (EDs). The review identifies key hormonal factors-serotonin, leptin, insulin, ghrelin, kisspeptin and cortisol-and their roles in the pathophysiology of PCOS and associated psychiatric symptoms.
View Article and Find Full Text PDFBranched-Chain Amino Acid (BCAA) Oligopeptide Determination from Whey Proteins: Preparation, Peptide Profiles, and Anti-Fatigue Activity.
Foods
December 2024
School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China.
Whey proteins have anti-fatigue activity, but there are few studies that have reported the ameliorative effects of branched-chain amino acid (BCAA) oligopeptides from whey proteins on fatigue in mice. The purposes of this study were to establish a process for the preparation of BCAA oligopeptides from whey protein and to investigate the anti-fatigue activity of BCAA oligopeptides. Whey proteins were hydrolyzed by trypsin and flavourzyme and purified by ethanol precipitation and reversed-phase high performance liquid chromatography (RP-HPLC).
View Article and Find Full Text PDFDiffuse Noxious Inhibitory Controls in Chronic Pain States: Insights from Pre-Clinical Studies.
Int J Mol Sci
January 2025
Instituto de Investigação e Inovação em Saúde da Universidade do Porto-i3S, R. Alfredo Allen 208, 4200-135 Porto, Portugal.
Diffuse noxious inhibitory control (DNIC), also known as conditioned pain modulation (CPM) in humans, is a paradigm wherein the heterotopic application of a noxious stimulus results in the attenuation of another spatially distant noxious input. The pre-clinical and clinical studies show the involvement of several neurochemical systems in DNIC/CPM and point to a major contribution of the noradrenergic, serotonergic, and opioidergic systems. Here, we thoroughly review the latest data on the monoaminergic and opioidergic studies, focusing particularly on pre-clinical models of chronic pain.
View Article and Find Full Text PDFThe Relationship Between Impulsivity Traits and In Vivo Cerebral Serotonin Transporter and Serotonin 2A Receptor Binding in Healthy Individuals: A Double-Tracer PET Study with C-11 DASB and C-11 MDL100907.
Int J Mol Sci
December 2024
Neuroscience Research Institute, Gachon University, Incheon 21565, Republic of Korea.
To elucidate the potential roles of presynaptic and postsynaptic serotonergic activity in impulsivity traits, we investigated the relationship between self-reported impulsiveness and serotonin transporter (5-HTT) and 5-HT2A receptors in healthy individuals. In this study, 26 participants completed 3-Tesla magnetic resonance imaging and positron emission tomography with [C]DASB and [C]MDL100907. To quantify 5-HTT and 5-HT2A receptor availability, the binding potential (BP) of [C]DASB and [C]MDL100907 was derived using the simplified reference tissue model with cerebellar gray matter as the reference region.
View Article and Find Full Text PDFLong-Term 5-HT Receptor Agonist NLX-112 Treatment Improves Functional Recovery After Spinal Cord Injury.
Int J Mol Sci
December 2024
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Spinal cord injury (SCI) results in functional deficits below the injured spinal level. The descending serotonergic system in the spinal cord is critically involved in the control of motor and autonomic functions. Specifically, SCI damages the projections of serotonergic fibers, which leads to reduced serotonin inputs and increased amounts of spinal serotonergic receptors.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!