<p>Valproic acid (VPA) is clinically utilized as an anti-convulsant and mood stabilizer, though its mechanism of action has not been fully elucidated.<strong> </strong>Evidence suggests an interaction between VPA and the melatonergic system as VPA up-regulated the melatonin MT<sub>1</sub> receptor subtype in rat C6 glioma cells. To determine if the observed effects can translate to an <em>in vivo </em>model, we investigated the effects of chronic VPA administration in a rat model on the expression of MT<sub>1</sub> and MT<sub>2</sub> receptors in the hippocampus. We also investigated the effect of chronic VPA treatment on the expression of the neurotrophic factors BDNF and GDNF in the rat hippocampus and striatum.</p> <p>(1) Animals were separated into two groups with the experimental group receiving VPA (4 mg/mL) for 17 days, and the control receiving vehicle. The hippocampus was dissected and MT<sub>1</sub>, MT<sub>2</sub>, BDNF and GDNF mRNA were analyzed with RT-PCR. (2) Animals were separated into three groups with the first group receiving VPA (4 mg/mL), the second receiving VPA (3 mg/mL) for 16 days, and the control receiving vehicle. MT<sub>2</sub> mRNA in the hippocampal subregions were analyzed with in situ hybridization.</p> <p>VPA induced the expression of MT<sub>1</sub> and MT<sub>2</sub> mRNA in the hippocampus in the experimental group compared to the control group. VPA also increased MT<sub>2</sub> mRNA expression in the subregions of the hippocampus. Additionally, BDNF and GDNF mRNA expression were increased in the VPA treatment group.</p> <p>These findings raise the interesting question of whether the diverse clinical effects of VPA involve an interaction with the melatonergic system.</p> / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/12901 |
| Date | 04 1900 |
| Creators | Sathiyapalan, Arani |
| Contributors | Niles, Len, Foster, Jane, Sakic, Boris, Medical Sciences (Neuroscience and Behavioral Science) |
| Source Sets | McMaster University |
| Detected Language | English |
| Type | thesis |
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