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.
Schiller
Edward D
ED
Department of Human Anatomy and Medical Neurobiology, College of Medicine, Texas A&M University System Health Science Center, College Station, TX 77843-1114, USA.
Champney
Thomas H
TH
Reiter
Cindy K
CK
Dohrman
Douglas P
DP
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008550:Melatonin / Q000494:pharmacology*; D009538:Nicotine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D016716:PC12 Cells; D037342:Pertussis Toxin / Q000008:administration & dosage; D051381:Rats
D018492:Dopamine Antagonists; D009538:Nicotine; D037342:Pertussis Toxin; D008550:Melatonin; D004298:Dopamine