Tác động của đối kháng thể thụ thể dopamine D1 hoặc D2 đối với các hiệu ứng tăng động và hiệu ứng kích thích phân biệt của (+)-MDMA

Psychopharmacology - Tập 173 - Trang 326-336 - 2004
Marcy J. Bubar1, Kami M. Pack1, Paul S. Frankel1, Kathryn A. Cunningham1
1Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, USA

Tóm tắt

Cả việc phóng thích dopamine (DA) và serotonin (5-HT) đều được kích thích bởi (+)-MDMA; tuy nhiên, có rất ít thông tin về sự đóng góp của các thụ thể DA D1 và D2 (tương ứng là D1R và D2R) trong các hiệu ứng hành vi của (+)-MDMA. Để kiểm tra giả thuyết rằng một đối kháng thể D1R hoặc D2R sẽ làm giảm bớt các hiệu ứng tăng động hoặc kích thích phân biệt của (+)-MDMA. Những con chuột đực Sprague-Dawley (n=164) đã được tiền điều trị với đối kháng thể D1R SCH 23390 (3.125–50 μg/kg, SC) hoặc đối kháng thể D2R eticlopride (12.5–50 μg/kg, SC) trước khi điều trị với (+)-MDMA (3 mg/kg, SC) và hoạt động locomotor đã được ghi lại bằng cách sử dụng các thiết bị theo dõi ánh sáng. Mười hai con chuột bổ sung đã được huấn luyện để phân biệt (+)-MDMA (1 mg/kg, IP) với nước muối trong một bài kiểm tra tăng cường nước FR20 với hai cần gạt, đã được cho SCH 23390 (6.25 μg/kg, IP) hoặc eticlopride (12.5 μg/kg, IP) trước khi dùng (+)-MDMA (0.375–1.0 mg/kg, IP). Sau đó, các con chuột được đưa vào các buồng phân biệt thuốc và tỷ lệ phản ứng thích hợp với (+)-MDMA và tỷ lệ phản ứng đã được đo. Cả SCH 23390 và eticlopride đều chặn sự tăng động do (+)-MDMA gây ra theo tỷ lệ liều; liều cao nhất của các đối kháng thể cũng hiệu quả trong việc ức chế hoạt động locomotor cơ bản. Ở những con chuột được huấn luyện để phân biệt (+)-MDMA với nước muối, SCH 23390 (6.25 μg/kg), nhưng không phải eticlopride (12.5 μg/kg), đã chặn các hiệu ứng kích thích của (+)-MDMA mà không làm thay đổi tỷ lệ phản ứng. Dữ liệu này cho thấy rằng DA được phóng thích một cách gián tiếp do tác dụng của (+)-MDMA dẫn đến kích thích các thụ thể D1R và D2R để tăng cường hoạt động locomotor. Hơn nữa, thụ thể D1R dường như đóng vai trò nổi bật hơn thụ thể D2R trong các đặc tính kích thích phân biệt của (+)-MDMA.

Từ khóa

#Dopamine #Thụ thể D1 #Thụ thể D2 #(+)-MDMA #Tăng động #Kích thích phân biệt

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