title: Brain changes associated with thromboxane receptor antagonist SQ 29,548 treatment in a mouse model.
abstract: The purpose of this study was to characterize behavioral and physiological effects of a selective thromboxane (TP) receptor antagonist, SQ 29,548, in the C57Bl/6 mouse model. At 6 months of age, male mice were given either sham or drug i.p. injections for 3 days at a dose of 2 mg/kg each day. On the day after the final injection, mice were subjected to behavioral testing before brain collection. Left hemisphere hippocampi were collected from all mice for protein analysis via Western blot. Right brain hemispheres were fixed and embedded in gelatin and then serially sectioned. The sections were immunostained with anti-c-Fos antibodies. Prostaglandin analysis was performed from remaining homogenized brain samples, minus the hippocampi. Injection of SQ 29,548 decreased selective brain prostaglandin levels compared with sham controls. This correlated with robust increases in limbic-region c-Fos immunoreactivity in the SQ 29,548-injected mice. However, drug-treated mice demonstrated no significant changes in relevant hippocampal protein levels compared with sham treatments, as determined from Western blots. Surprisingly, injection of SQ 29,548 caused mixed changes in parameters of depression and anxiety-like behavior in the mice. 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. Whether the drug affects neurons directly or through a secondary pathway involving endothelium or other tissues remains unclear.
authors.affiliation: Department of Biology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Rebel
authors.affiliation: Department of Biology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota.
authors.forename: Siri A
authors.initials: SA
authors.lastname: Urquhart
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota.
authors.forename: Kendra L
authors.initials: KL
authors.lastname: Puig
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota.
authors.forename: Atreyi
authors.initials: A
authors.lastname: Ghatak
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Brose
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota.
authors.forename: Mikhail Y
authors.initials: MY
authors.lastname: Golovko
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota.
authors.forename: Colin K
authors.initials: CK
authors.lastname: Combs
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003863:Depression / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D017482:Receptors, Thromboxane; C045749:SQ 29548
keywords: anxiety; c-Fos; depression; thromboxane; thromboxane receptor