Korean J Physiol Pharmacol.  1998 Dec;2(6):671-676.

Effects of dopamine and haloperidol on morphine-induced CREB and AP-1 DNA binding activities in differentiated SH-SY5Y human neuroblastoma cells

Affiliations
  • 1Department of Pharmacology and Institute for Medical Science, Keimyung University School of Medicine, Taegu 700-712, Korea.

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.

Keyword

CREB; AP-1; Morphine tolerance; SH-SY5Y Cells

MeSH Terms

Cyclic AMP Response Element-Binding Protein
DNA*
Dopamine*
Haloperidol*
Humans*
Morphine
Neuroblastoma*
Transcription Factor AP-1*
Transcription Factors
Cyclic AMP Response Element-Binding Protein
DNA
Dopamine
Haloperidol
Morphine
Transcription Factor AP-1
Transcription Factors
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