Angelucci Francesco, Gruber Susanne H M, El Khoury Aram, Tonali Pietro Attilio, Mathé Aleksander A
Karolinska Institutet, Clinical Neuroscience, Psychiatry M56, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden.
Eur Neuropsychopharmacol. 2007 Dec;17(12):756-62. doi: 10.1016/j.euroneuro.2007.03.002. Epub 2007 Apr 16.
Amphetamines (methamphetamine and d-amphetamine) are dopaminergic and noradrenergic agonists and are highly addictive drugs with neurotoxic effect on the brain. In human subjects, it has also been observed that amphetamine causes psychosis resembling positive symptoms of schizophrenia. Neurotrophins are molecules involved in neuronal survival and plasticity and protect neurons against (BDNF) are the most abundant neurotrophins in the central nervous system (CNS) and are important survival factors for cholinergic and dopaminergic neurons. Interestingly, it has been proposed that deficits in the production or utilization of neurotrophins participate in the pathogenesis of schizophrenia. In this study in order to investigate the mechanism of amphetamine-induced neurotoxicity and further elucidate the role of neurotrophins in the pathogenesis of schizophrenia we administered intraperitoneally d-amphetamine for 8 days to rats and measured the levels of neurotrophins NGF and BDNF in selected brain regions by ELISA. Amphetamine reduced NGF levels in the hippocampus, occipital cortex and hypothalamus and of BDNF in the occipital cortex and hypothalamus. Thus the present data indicate that chronic amphetamine can reduce the levels of NGF and BDNF in selected brain regions. This reduction may account for some of the effects of amphetamine in the CNS neurons and provides evidences for the role of neurotrophins in schizophrenia.
苯丙胺类药物（甲基苯丙胺和右旋苯丙胺）是多巴胺能和去甲肾上腺素能激动剂，是具有高度成瘾性且对大脑有神经毒性作用的药物。在人类受试者中，还观察到苯丙胺会导致类似于精神分裂症阳性症状的精神病。神经营养因子是参与神经元存活和可塑性的分子，可保护神经元免受损伤。脑源性神经营养因子（BDNF）是中枢神经系统（CNS）中含量最丰富的神经营养因子，是胆碱能和多巴胺能神经元的重要存活因子。有趣的是，有人提出神经营养因子产生或利用方面的缺陷参与了精神分裂症的发病机制。在本研究中，为了探究苯丙胺诱导的神经毒性机制，并进一步阐明神经营养因子在精神分裂症发病机制中的作用，我们给大鼠腹腔注射右旋苯丙胺8天，并通过酶联免疫吸附测定法（ELISA）测量选定脑区中神经营养因子NGF和BDNF的水平。苯丙胺降低了海马体、枕叶皮质和下丘脑的NGF水平以及枕叶皮质和下丘脑的BDNF水平。因此，目前的数据表明，慢性苯丙胺可降低选定脑区中NGF和BDNF的水平。这种降低可能解释了苯丙胺对中枢神经系统神经元的部分作用，并为神经营养因子在精神分裂症中的作用提供了证据。
