Effects of Dopamine and Haloperidol on Morphine-induced CREB and AP-1 DNA Binding Activities in Differentiated SH-SY5Y Human Neuroblastoma Cells

• 영문명: Effects of Dopamine and Haloperidol on Morphine-induced CREB and AP-1 DNA Binding Activities in Differentiated SH-SY5Y Human Neuroblastoma Cells
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Soo-kyung Kim Gee-youn Kwon
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제2권 제6호, 671~676쪽, 전체 6쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 1998.01.01

영문 초록

In the present study, we first examined whether the changes in the DNA binding activities of the transcription factors, cAMP response element binding protein (CREB) and activator protein-1 (AP-1) mediate the long-term effects of morphine in differentiated SH-SY5Y human neuroblastoma cells. The increases in CREB and AP-1 DNA binding activities were time-dependent up to 6 days of morphine treatment (1, 4, and 6 days). However, the significant reduction in the DNA binding activities of CREB and AP-1 was observed after 10 days of chronic morphine (10 μM) administration. Secondly, we examined whether the changes of CREB and AP-1 DNA binding activities could be modulated by dopamine and haloperidol. Dopamine cotreatment moderately increased the levels of the CREB and AP-1 DNA binding activities induced by 10 days of chronic morphine treatment, and haloperidol cotreatment also resulted in a moderate increase of the CREB and AP-1 DNA binding activities. However, dopamine or haloperidol only treatment showed a significant increase or decrease of the CREB and AP-1 DNA binding activities, respectively. In the case of acute morphine treatment, the CREB and AP-1 DNA binding activities were shown to decrease in a time-dependent manner (30, 60, 90, and 120 min). Taken these together, in differentiated SH-SY5Y cells, morphine tolerance seems to involve simultaneous changes of the CREB and AP-1 DNA binding activities. Our data also suggest the possible involvement of haloperidol in prevention or reversal of morphine tolerance at the transcriptional level.

키워드

CREB AP-1 Morphine tolerance SH-SY5Y Cells