Melatonin inhibition of nicotine-stimulated dopamine release in PC12 cells

Melatonin, a pineal hormone, modifies numerous physiologic processes including circadian rhythms and sleep. In specific tissues, melatonin appears to have an inverse relationship with dopamine. To examine this relationship, a pheochromocytoma cell line (PC12) was used to determine the extent of melatonin's ability to inhibit nicotine-stimulated dopamine release. Multiple experiments were conducted that examined: (1). the dose response of acute melatonin (5 min); (2). the effects of chronic melatonin (16 h pre-exposure); (3). the effects of prior nicotine or melatonin exposure (5 min) on melatonin's ability to alter dopamine release from a second 5-min nicotine exposure; and (4). the role of melatonin receptors (by pertussis toxin inhibition) on nicotine-stimulated dopamine release. In the dose response studies, melatonin inhibited nicotine-stimulated dopamine release with an ED50 of 8.6 microM. Chronic exposure to melatonin had no effect on melatonin's acute inhibition of nicotine-stimulated dopamine release. Prior nicotine or melatonin exposure had little effect on subsequent melatonin or nicotine exposure, except that the cells exposed to nicotine were not responsive to a second exposure to nicotine. Blockade of melatonin receptor function by pre-exposure to pertussis toxin (16 h) did not prevent melatonin's inhibition of nicotine-stimulated dopamine release. However, the toxin-treated cells were less inhibited by melatonin when compared to control cells suggesting a partial role for melatonin receptors. These results indicate that melatonin can acutely inhibit nicotine-stimulated dopamine release in PC12 cells. This model system allows detailed examination of melatonin's cellular actions as well as supporting a role for melatonin on neuronal dopamine release.