For example, a 1983 clinical study by Lieb et al. The increased inflammatory state associated with platelet activation may well include changes in pro-aggregation PG production. These receptors are of particular interest, as they might be therapeutically targeted to treat a wide variety of inflammation-related conditions.Īlthough it remains mechanistically unclear as well as somewhat controversial, numerous studies continue to report a positive correlation between increased platelet activation and depression in humans ( Aschbacher et al. These effects are mediated through a multitude of prostanoid receptors of varying binding specificity ( Eglen and Whiting 1988). In general, PG that are produced from this reaction are either pro-inflammatory or anti-inflammatory in nature, and elicit their effects in a wide variety of tissues. TXA 2 and other prostanoids (PG) are formed when arachidonic acid is released from the phospholipid bilayer and metabolized by cyclooxygenases ( Simmons et al. It is well known that thromboxane A 2 (TXA 2) is a potent stimulus of platelet activation which causes changes in platelet shape, aggregation, and secretion ( Hamberg et al. Whether the drug affects neurons directly or through a secondary pathway involving endothelium or other tissues remains unclear. In conclusion, the results indicate that administration of peripheral TP receptor antagonists alters brain levels of prostanoids and influences neuronal activity with only minimal alterations of behavior. Surprisingly, injection of SQ 29,548 caused mixed changes in parameters of depression and anxiety-like behavior in the mice. However, drug treated mice demonstrated no significant changes in relevant hippocampal protein levels compared to sham treatments, as determined by western blots. This correlated with robust increases in limbic region c-Fos immunoreactivity in the SQ 29,548 injected mice. Injection of SQ 29,548 decreased selective brain prostaglandin levels compared to sham controls. Prostaglandin analysis was performed from remaining homogenized brain samples, minus the hippocampi. The sections were immunostained using anti-c-Fos antibodies. Right brain hemispheres were fixed and imbedded in gelatin, and serially sectioned. Left hemisphere hippocampi were collected from all mice for protein analysis via western blot. On the day after the final injection mice were subjected to behavioral testing paradigms before brain collection. At six months of age, male mice were given either sham or drug intraperitoneal injections for three days at a dose of 2mg/kg each day. The purpose of this study was to characterize behavioral and physiological effects of a selective thromboxane receptor (TP) antagonist, SQ 29,548, in the C57BL/6 mouse model.
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