کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2013548 1067121 2008 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Involvement of neurosteroids in the anxiolytic-like effects of AC-5216 in mice
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Involvement of neurosteroids in the anxiolytic-like effects of AC-5216 in mice
چکیده انگلیسی

AC-5216, a ligand for the translocator protein (18 kDa) (TSPO), previously called the peripheral benzodiazepine receptor (PBR), produces anxiolytic-like effects mediated by TSPO in animal models of anxiety. Since stimulation of TSPO is considered to promote the synthesis of neurosteroids, we investigated the possible role of endogenous neurosteroids that positively act on the GABAA receptor in the anxiolytic-like effects of AC-5216. In our experiments, the effects of trilostane and finasteride, two inhibitors of steroidogenic enzymes, and picrotoxin, a GABAA receptor-gated Cl− channel blocker, on the anxiolytic-like effects of AC-5216 were examined in the social interaction test in mice. Also, the anxiolytic-like effects of allopregnanolone and progesterone were examined. The anxiolytic-like effects of AC-5216 (0.1 mg/kg, p.o.) were inhibited by trilostane (10–30 mg/kg, s.c.), finasteride (10–30 mg/kg, s.c.), and picrotoxin (0.03–0.3 mg/kg, s.c.), while those of diazepam (0.1 mg/kg, p.o.) were inhibited by picrotoxin only. The anxiolytic-like effects of progesterone (1–3 mg/kg, s.c.) were inhibited by finasteride (3–30 mg/kg) and picrotoxin (0.1–0.3 mg/kg), although those of allopregnanolone (10 mg/kg, s.c.) were inhibited by picrotoxin only. These results demonstrate that the anxiolytic-like effects of AC-5216 are due to newly synthesized neurosteroids that enhance GABAA receptor function.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacology Biochemistry and Behavior - Volume 89, Issue 2, April 2008, Pages 171–178
نویسندگان
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