Melatonin is a naturally secreted hormone which could be found in animals, plants and microbes. In animals, its circulating level varies around the clock. As a FDA approved diet supplement, it has been used in sleep disorder, depression, aging, immunity disorder, autism, etc, with little known side effects. Now, scientists found that melatonin could also be a potential candidate in drug addiction treatment.
Drug addiction is a chronic brain disease and somehow quite difficult for a large proportion of abusers to completely walk out of its shadow due to the high rates of relapse. For example, a patient who has been maintained physically substances clean for 20 years almost could not resist his drug craving while he was imposed to the once familiar substances-experience related environment again. In medical history, although there are many hypotheses and interventions to try to fight with drug addiction, either physically or physiologically, but the effective methods with minor side effects are still to be discovered.
Mitochondria have been known as the “powerhouse of cell” and are enriched in growth cones, axon terminals and dendrites of neurons with importance in regulating neurite outgrowth and synaptic plasticity in the mature nervous system. Meanwhile, mitochondrial dysfunction and abnormality are hallmarks of many brain disorders. So, the research team of Prof. YAO Yonggang and XU Lin (Kunming Institute of Zoology, CAS) has conducted a study to try to figure out the possible connections between mitochondria and drug addiction.
“We have noticed that the lower mtDNA copy numbers is a common phenomenon, and it has been validated in hippocampus, peripheral blood of chronic morphine treated mice and rats as well as heroin addicted patients”, according to YAO and XU.
Based on their observation and the fact that DNA damage and mitochondrial dysfunction can trigger autophagy, YAO and XU’s research team has hypothesized that dysfunctional mitochondria induced by opiate-mediated neurotoxicity could be degraded by autophagy and eventually lead to neuronal pathological remodeling and plasticity. Then, following this hypothesis, prevention of the reduction of mtDNA copy number might be beneficial to the clinical treatment of addiction.
Well, as the main secretory product of the pineal gland that regulates circadian rhythms and capable of inhibiting autophagy through a redox-mediated mechanism, weather melatonin could relieve the deleterious effects of opiate during addiction have been tested in their study. The results indicated that melatonin could rescue morphine-induced autophagy and ameliorate decreased mtDNA copy number in response to morphine treatment in cultured cells and neurons and in a mouse model of morphine addiction. Moreover, the pretreatment with melatonin has significantly prevented morphine-induced behavioral sensitization and analgesic tolerance.
“Although we still missing pieces of this complex puzzle of morphine, mitochondria, autophagy, and synaptic plasticity, our findings strongly support the positive role melatonin has played in helping the addicted patients to recover from opioid withdrawal. Meanwhile, it is quite inspiring in seeking the new solutions of drug addiction treatment”, YAO and XU said.
Details of this study could be obtained from Autophagy(http://www.landesbioscience.com/journals/autophagy/article/25468/).
(By Su-Qing Liu)
