Effects of dopamine and haloperidol on morphine-induced CREB and AP-1 DNA binding activities in differentiated SH-SY5Y human neuroblastoma cells.
- Author:
Soo Kyung KIM
1
;
Gee Youn KWON
Author Information
1. Department of Pharmacology and Institute for Medical Science, Keimyung University School of Medicine, Taegu 700-712, Korea.
- Publication Type:Original Article
- Keywords:
CREB;
AP-1;
Morphine tolerance;
SH-SY5Y Cells
- MeSH:
Cyclic AMP Response Element-Binding Protein;
DNA*;
Dopamine*;
Haloperidol*;
Humans*;
Morphine;
Neuroblastoma*;
Transcription Factor AP-1*;
Transcription Factors
- From:The Korean Journal of Physiology and Pharmacology
1998;2(6):671-676
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 muM) 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.
