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Điều chỉnh sự giải phóng dopamine ở vùng nhân đuôi bởi các chất đối kháng thụ thể 5-HT2A và 5-HT2C: Các nghiên cứu PET [11C]raclopride trên chuột
Tóm tắt
Sự đối kháng tại các thụ thể serotonin 5-HT2A và 5-HT2C điều chỉnh sự giải phóng dopamine (DA) ở vỏ não và vùng nhân đuôi có thể là nguyên nhân của một số khía cạnh hiệu quả lâm sàng của các hợp chất chống loạn thần ‘không điển hình’. Tuy nhiên, chưa có thông tin liệu việc điều chỉnh sự giải phóng DA trung gian bởi thụ thể 5-HT2A/2C có thể được định lượng bằng hình ảnh hóa thần kinh phi xâm lấn hay không, như cần thiết để điều tra các quá trình này ở người. Mục tiêu của nghiên cứu là thực hiện một nghiên cứu khả thi trên chuột để xác định xem việc điều chỉnh bởi thụ thể 5-HT2A/2C của sự giải phóng DA có thể được quan sát bằng hình ảnh điện toán phát positron (PET) hay không. Các con chuột được tiêm hoặc dung dịch kiểm soát, một chất đối kháng 5-HT2A/2C kết hợp (ketanserin, 3 mg/kg i.p.), hoặc chất đối kháng 5-HT2C chọn lọc hơn là SB 206,553 (10 mg/kg i.p.) 30 phút trước khi tiêm chất quét PET DA D2 [11C]raclopride (∼11 MBq) và sau đó được quét trong 60 phút bằng một máy quét động vật nhỏ bốn buồng độ dày cao. Sử dụng cùng một kỹ thuật, việc điều chỉnh sự giảm [11C]raclopride do amphetamine (4 mg/kg) gây ra bởi sự đối kháng 5-HT2A (SR 46349B, 0.2 mg/kg i.v.) cũng được xác định. Phù hợp với việc gia tăng sự giải phóng DA được đo bởi những người khác sử dụng viêm mạch, sự đối kháng 5-HT2C làm giảm đáng kể sự gắn kết [11C]raclopride ở vùng nhân đuôi (p < 0.003), trong khi những giảm do amphetamine gây ra ở sự gắn kết [11C]raclopride ở vùng nhân đuôi (p < 0.001) bị giảm nhẹ sau khi tiêm chất đối kháng 5-HT2A (p = 0.04). Những kết quả này cung cấp thông tin về khả năng giám sát sự điều chỉnh của hệ thống DA trung gian bởi thụ thể 5-HT2A/2C ở người bằng việc sử dụng PET và, nói chung hơn, cho thấy rằng hình ảnh PET với thuốc đánh dấu D2 có thể được sử dụng để giám sát hiệu quả của các chất điều chỉnh DA mới trong việc giảm thiểu sự giải phóng DA kích thích.
Từ khóa
#thụ thể serotonin #5-HT2A #5-HT2C #dopamine #đối kháng #hình ảnh PET #chuộtTài liệu tham khảo
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