Stimulatory effect of morphine on rat pineal melatonin synthesis via a cyclic AMP-dependent transcription pathway

The expression of mRNA of opioid receptors and the existence of opioid binding site in the rat pineal gland have been demonstrated previously. A major finding was that morphine enhanced the activity of the rate-limiting enzyme, N-acetyltransferase (NAT) and increased the level of melatonin in rat pineal gland. An attempt has been made in order to clarify the mechanism of this induction. In the present study, the stimulatory effect of morphine on the expression of NAT mRNA in the rat pineal gland has been demonstrated using semi-quantitative RT-PCR technique. The results showed that both acute and chronic morphine treatments significantly increased NAT mRNA expression in rat pineal gland. In addition, the effect of morphine on the phosphorylation of the transcription factors, cyclic AMP responsive element-binding protein (CREB) was investigated. Western blot analysis showed that morphine significantly increased phosphorylation of CREB. These results indicate that at least one downstream messenger pathway for the activation of opioidergic system on the induction of melatonin synthesis in the rat pineal gland acts via cyclic AMP-dependent cascade and transcription mechanism.