| Background: Addictive substances are usually divided into opiates (eg. morphine and heroin ), psychoactive agents (such as cocaine), and ethanol. The consumption of alcohol, one of the addictive substances, which can be obtained most easily, is appalling and becoming into the widespread abuse. Alcoholism, alcohol abuse are major world-wide social problems. A number of studies indicated a link between the occurrence of the violence, traffic accident, divorce to alcohol dependence, and abuse. In additon, the medical complications of excessive dinking have become the third health problem, which is second only to the cardiovascular diseases and tumors. Therefore, to investigate the pathophysiology of alcohol dependence at a cellular and molecular level, is of medical importance and social significance.As all know, alcohol has some similar effects to opiates and psychoactive agents, such as euphoria, tolerance and dependence, withdrawal syndromes after cessation of chronic drug administration. Prolonged, heavy drinking will result in both physical and psychological dependenc as well as a variety of body diseases. The development of alcohol dependence is usually associated with the physiologic tolerance. Once formed, it may result in increased alcohol intake in an effort to maintain the drug effect and to avoid the affliction from alcohol withdrawal syndromes. So, alcohol dependence can be defined as the intense drug craving, or the loss ofcontrol over seeking and taking of drugs. Although drugs of abuse are chemically divergent molecules with very different initial activities and receptors, the resultant addictions share many important features. Prominent feature among these actions is the activation of the mesolimbic dopamine reward system in which the ventral tegmantal area (VTA) of the midbrain-ventral striatum (nucleus accumbens, NAcc)-frontal cortex is of particular importance in drug addiciton.The mechanisms of physical dependence caused by drug abuse have been most developed and there are effective therapies on it. However, we still have no effective treatments on subjective craving and high rates of relapse caused by repeated exposure to an addictive drug. Some recent evidence indicates that chronic administration of an addictive drug would eventually lead to changes in nuclear function and to altered rates of transcription of particular target genes by causing perturbation of intracellular signal transduction pathways; Alterd expression of these genes would lead to activity of the neurons in which those changes occur and, ultimately, to changes in the neural circuits in which those neurons operate. The result would be stable changes in behavior. Datas from investigations on opiate addiction indicated some genes involving drug reward, prominent genes of these are the gene transcription factors, such as the cAMP response element binding protein (CREB), and CRE-modulatory genes. However, the past researches on ethanol dependence (including our researches from 1990 to today ) focused principally on the neuronal adaptations which occur during ethanol administration, such as changes in the neuronal activity, alterations in endogenous opioids and receptors in the brain, and the interaction with other neurotransmitters. The molecular mechanisms of the addictive properties of ethanol are poorly investigated. Especially, little is knwn about the role of CREB in the brain rewarding system (eg. nucleus accumbens, and cortex)during ethanol dependenc.In addition, it is thought highly of that repeated exposure to addictive substances lead to damages in endocrine system. It is suggested that the disturbance of endocrine system may be the most general and serious lesions induced by the opiate dependence. But the opiate withdrawal syndrome may be a kind of special stress response, which appears to result, at least in part, from the stress abilities opposite to adaptations that occur during drug administration. Etanol also effects the function of endocrine system. However, the link between ethanol dependence...
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