AI Article Synopsis
- The GABA system is crucial in understanding anxiety and mood disorders, and this study examines tiagabine, a GABA transporter-1 inhibitor, for its potential anxiolytic and antidepressant effects.
- Acute administration of tiagabine and paroxetine showed positive effects in anxiety and depression tests, while chronic tiagabine treatment alone maintained these benefits over 22 days.
- Additionally, tiagabine treatment was linked to reduced levels of stress hormones and changes in gene expression related to stress response, suggesting it may help regulate the HPA (hypothalamic-pituitary-adrenal) system.
Article Abstract
Gamma-aminobutyric acid (GABA) system plays a pivotal role in the pathophysiology of anxiety and mood disorders. This study was aimed to assess the anxiolytic and antidepressant-like properties of tiagabine, an inhibitor of the GABA transporter-1 (GAT-1), after acute and chronic administration in C57BL/6JOlaHsD mice with paroxetine as a positive control. In first experiments, the acute administration of tiagabine (7.5 mg/kg, orally [PO]) and paroxetine (10 mg/kg PO) induced anxiolytic effects in the elevated plus maze test and the modified hole board test and an antidepressant-like effect in the forced swim test. Chronic application of tiagabine (7.5 mg/kg PO) and paroxetine (10 mg/kg PO) for 22 days revealed an anxiolytic and antidepressant-like efficacy of tiagabine only. In a further experiment, we analysed the impact of chronic tiagabine versus paroxetine treatment on the hypothalamic-pituitary-adrenocortical (HPA) system regulation. GAT-1 blockade induced a setpoint-shift of the stress hormone system toward lower levels as indicated by decreased plasma corticosterone concentrations and attenuated gene expression levels of corticotropin-releasing factor in the paraventricular nucleus of the hypothalamus and of hippocampal steroid receptors. This data indicate that both acute and long-term anxiolytic and antidepressant-like properties of brain GAT-1 inhibition coincide with a reduction in HPA system activity in mice.
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| http://dx.doi.org/10.1177/0269881109103091 | DOI Listing |
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