| Objective : Drug dependence is a chronic, relapsing disease, characterized by compulsive drug seeking and use and by neurochemical and molecular changes in the brain.The powerful and uncontrollable desire for drugs often make the addict use the drug continually regardless of the damage to their body. In our country the drug of abuse is mostly the material of opioid type. The mechanism of drug dependence not only involve endogenous opioid peptides, opioid receptor and its signal transduction, but also involve the adaptability changes of other neurotransmitters and their signal transduction. The cyclic AMP(cAMP) and cyclic GMP(cGMP), as important second messengers, play a vital role in producing drug tolerence and dependence. There are a lot of brain regions and neurotransmitters involved in the morphine physical depentent, including the glutaminic acid nervous system and gamma-aminobutyric acid nervous system. Melatonin(MT), acting as a nerve endocrine hormone, has an important function to maintain the physiological homeostasis in brain. The research in the past showed MT could effectively block the development of physical dependence on morphine or heroin in mice, but the concrete mechanism remains unclear. This study investigated the effects of MT on withdrawal syndrome in morphine dependent rats and the contents of cAMP, cGMP, Glu and GABA in the brain in order to clarify the possible mechanisms of MT attenuating morphine withdrawal syndrome. Methods: 100 healthy Wistar rats, half male and half female, weighting 250-280g, were randomly divided into six groups: control group(NS group), morphine depentent group (MOR group), naloxone withdrawal group(NAL group), three different dosage(25 mg·kg-1,50mg·kg-1 and 100mg·kg-1) MT treatment group(MT25, MT50, MT100). The drug dependence model in rats was established by subcutaneous injection of five different dosage(10,20,30,40,50 mg·kg-1) of morphine for 5 days. Withdrawal syndromes were induced by intraperitoneal injection of naloxone (5mg·kg-1), the intensity of withdrawal syndrome was evaluated according to the number of jumping and the body weight loss. Rats were anesthetized and the brain was taken to get involved brain regions after experiment. The contents of cAMP and cGMP were measured by radioimmunoassay (RIA), the level of Glu and GABA was detected by high performance liquid chromatography(HPLC).The results of experiment were analyzed with SPSS statistics software, and a level of P<0.05 was considered statistically significant.Results1 Effects of MT on withdrawal syndrome in morphine dependent rats 1.1 Effects of MT on the number of jumping in morphine withdrawal rats The number of jumping of morphine dependent rats with naloxone precipitation was obviously increased compared with MOR group(P<0.01). In the MT25, MT50 and MT100 group the number of jumping was decreased in a dose-dependent manner (P<0.01). These results demonstrated that three different dosage(25 mg·kg-1, 50mg·kg-1 and 100mg·kg-1) MT could significantly inhabit jumping reaction of morphine dependent rats with naloxone precipitation a dose-dependent manner.1.2 Effects of MT on the body weight loss in morphine dependent rats with naloxone precipitation The body weight loss of NS group and MOR group was 0.9±0.57g and 1.1±0.57g respectively. The rats of NAL group lost more weight than MOR group (12.1±3.0g,P<0.01). The body weight loss of MT25, MT50 and MT100 group was obviously reduced(10.2±2.97g, 7.5±1.27g and 5.1±2.56g, P<0.01 or P<0.05 vs NAL group). These results demonstrated that three different dosage(25 mg·kg-1, 50mg·kg-1 and 100mg·kg-1) MT could reduce the body weight loss after naloxone precipitation.2 Effects of MT on the cAMP and cGMP contents of diencephalons and prefrontal cortex in different groups2.1 Effects of MT on the cAMP content of diencephalons and prefrontal cortex in different groups Increase of the cAMP content in diencephalons was observed in MOR group (P<0.01 vs NS group). In NAL group there was no significant a...
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