Ron Dorit, Janak Patricia H
Ernest Gallo Research Center, Department of Neurology, University of California, San Francisco, Emeryville, USA.
Rev Neurosci. 2005;16(4):277-85. doi: 10.1515/revneuro.2005.16.4.277.
Biochemical adaptations to drugs of abuse and alcohol are especially profound in midbrain dopaminergic neurons. Long-lasting molecular and structural changes in mesolimbic dopaminergic neurons that result from chronic exposure to drugs of abuse and alcohol are thought to underlie adverse behaviors such as compulsive drug seeking and relapse. Recent studies suggest that a subset of these changes is prevented/reversed by activation of the glial cell line-derived neurotrophic factor (GDNF) signaling pathway. Behavioral effects of drugs of abuse such as cocaine and alcohol are also negatively regulated by GDNF: inhibition of the endogenous GDNF pathway enhances the activity of drugs of abuse, while administration of GDNF reduces the severity of the effects. In this review, we summarize the data implicating GDNF as a negative regulator of drug and alcohol addiction. We also provide evidence to suggest that therapies that activate GDNF signaling may be useful for the treatment of drug and alcohol addiction.
对滥用药物和酒精的生化适应在中脑多巴胺能神经元中尤为显著。长期接触滥用药物和酒精导致的中脑边缘多巴胺能神经元持久的分子和结构变化被认为是强迫性觅药和复发等不良行为的基础。最近的研究表明，这些变化中的一部分可通过激活胶质细胞系源性神经营养因子（GDNF）信号通路来预防/逆转。可卡因和酒精等滥用药物的行为效应也受到GDNF的负调控：抑制内源性GDNF通路会增强滥用药物的活性，而给予GDNF则会减轻其效应的严重程度。在本综述中，我们总结了表明GDNF作为药物和酒精成瘾负调节因子的数据。我们还提供证据表明，激活GDNF信号的疗法可能对药物和酒精成瘾的治疗有用。
