| Drug dependence is a chronic, relapsing disease in brain, and compulsive drug-seeking and drug-taking behavior persist despite serious negative consequences, which induces adaptive changes in the central nervous system that lead to tolerance, physical dependence, sensitization, craving, and relapse at last. Drug abuse and dependence poses serious health, social, and economic problems around the world. Opiates are one of the most widely abused illegal drugs in the world and especially used in its traditional regions in Asia. In our country abused illegal opiates are mostly the morphine and heroin. The etiological agent of opioid substance is an exogenous opioid compound and the target is opioid receptors. A series after-effects produced by the action of the etiological agent on the targets involve dysfunction of many systems of the organism.Currently the most common treatment for opioid addicts is still gradual-reduction substitutes using an opioid agonist and symptom-specific therapy. However, this method actually uses another opiates (a morphine simulator) to substitute previous opioid and gradually reduce patients' craving and pain in the withdrawal process, it does not really solve the problem of the potential addictive effects of the substituting substance. In addition, this treatment may result in new addiction for it. Therefore, this may be not a ideal way to treat drug addiction. Symptom-specific therapy means that physicians treat withdrawal symptoms using anxiolytics, antidepressants, or relaxants. But those drugs have side effects in the long run. Therefore, modern medical science has the challenging task of finding a safe and effective drug to treat addiction from detoxification to rehabilitation. Melatonin (MT) is a hormone secreted cyclically from pineal gland and keeps human and animals in sync with the rhythms of the day and the season, and can also exert hypnotic, analgesic, anti-oxidant, anti-stress, anti-aging, anti-cancer and immunomodulatory effects. MT could attenuate effects of psychical and physical dependence induced by morphine and itself psychical and physical dependence have not been found, and the mechanism is not clear. Thus, to investigate the effects of MT on the messagers of cAMP, cGMP, CREB and CaMKⅡ, and on the gene expression of mAChR induced by naloxone in related brain regions of morphine dependent rats, the models of morphine dependent rats was established by subcutaneous injection of morphine in gradually increasing doses and the withdrawal syndrome were precipitated with naloxone. The aim is to clarify the molecular mechanism of the inhibitory effect of MT on morphine abstinence syndrome.Methods and results1 The inhibitory effect of MT on the physical and psychic dependence of morphine dependent rats(1) The inhibitory effect of MT on the naloxone-precipitated syndrome of morphine dependent ratsSeventy Wistar rats, half female and half male, weighing between 180g to 230g were used. The rats were randomly divided into seven groups with one of ten rats: normal saline control group (NS group), morphine dependent group (MOR group), naloxone precipitated withdrawal group (NAL group), MT25mg·kg-1 treatment group (MT25 group), MT50mg·kg-1 treatment group (MT50 group), MT100 mg·kg-1 treatment group (MT100 group) and MT25 mg·kg-1 combined with MOR group (mMT25). To observe the effects of MT on withdrawal symptoms of morphine dependent animals, the model of morphine physical dependent rats was established by subcutaneous injection of morphine in gradually increasing doses for 5 days (from 10 to 50mg·kg-1,two times daily). The withdrawal syndrome was precipitated by naloxone (5mg·kg-1, ip) and treated with MT in various doses 30 min before naloxone-precipitated withdrawal. The withdrawal syndrome and body weight loss were observed respectively. These data were presented as (s and analyzed with ANOVA and least significant difference (LSD) using SPSS statistical program. P<0.05 was considered statistically significant. Results: (1) Naloxone ip inject...
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