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Zhi-Bi Zhang,1 Tian-Yong Xu,2 Ding-Yun You,3 Shuai Yi,4 Qing Liu,4 Huifang-Jie Li,4 Jin-Yun Gu5 1Biomedical Engineering Center, Kunming Medical University, Kunming, People’s Republic of China; 2Experiment Center for Medical Science Research, Kunming, People’s Republic of China; 3Department of Science and Technology, Kunming Medical University, Kunming, People’s Republic of China; 4School of Forensic Medicine, Kunming Medical University, Kunming, People’s Republic of China; 5Zhanyi Branch of Qujing Public Security Bureau, Qujing, People’s Republic of China Background: A number of studies have demonstrated the significant and rapid antidepressant effects of ketamine, which is also known as a neurotoxic and illicit drug. Ketamine and alcohol are increasingly used together in clubs by teenagers and young adults. Previous studies have proven that chronic ketamine consumption induces a delayed and persistent activation of the dopamine (DA) system. However, the rewarding properties of recreational ketamine abuse remain unclear, and the underlying mechanisms of the effects on the DA system after administration of ketamine with ethanol are yet to be explored. Methods: Here, we evaluated the effects of two different doses of ketamine (30 mg/kg and 60 mg/kg) with and without ethanol (0.3156 g/kg) on DA concentration in the rat’s ventral tegmental area (VTA), a vital region in the reward and motivation system. We explored the effects of the combined drug treatment on the expression profiling of the DA metabolism genes, tyrosine hydroxylase, dopa decarboxylase, vesicular monoamine transporter 2, and synaptosomal-associated protein 25, as well as protein expression level of brain-derived neurotrophic factor in the rat’s VTA. Results: We found that administration of ketamine with ethanol led to a significant increase of DA in the VTA associated with differential regulation of mRNA levels of the four DA metabolism genes and protein levels of brain-derived neurotrophic factor. Moreover, the rewarding properties of coadministration of ketamine and ethanol were related to dopaminergic neuron activation in the VTA. Conclusion: These results indicated the possibility that combined drug treatment might positively affect the mesencephalic DA reward system. Keywords: ketamine, ethanol, TH, DDC, dopamine, ventral tegmental area

OBJECTIVES: to compare the acute and chronic effects of ethanol on the neural development, by analysis of the ontogenetic neural structure of mammals. METHODS: searches were performed in the following electronic databases: MEDLINE, SciElo, PubMed, LILACS, CAPES periodical, and the Open Journal System. The descriptors used were: "chronic ethanol toxicity", "chronic alcohol toxicity", "acute ethanol toxicity", "acute alcohol", "neural ontogenic development", "neuronal migration disturbances", "neural structure". The following inclusion criteria were used: articles published between 2003 and 2007, some classic articles in the field and an important neuropsychology textbook. RESULTS: the analysis of papers revealed that, although several studies of the chronic effects of ethanol exposure on the mammalian nervous system have been conducted, only a few have investigated the acute effects of ethanol on specific days of gestation, and these studies have revealed important disorders relating to the cerebral tissue. CONCLUSIONS: it should be recommended that women refrain from the consumption of ethanol during gestational phase to protect the fetus' health. Furthermore, the acute consumption of ethanol by women nearing the eighth or ninth week of gestation has been shown to be potentially harmful to the nervous tissue of the fetus.OBJETIVOS: comparar os efeitos agudo e crônico do etanol sobre o desenvolvimento do sistema nervoso através da análise da estrutura ontogênica neural dos mamíferos. MÉTODOS: pesquisas foram feitas nas bases eletrônicas: MEDLINE, SciElo, PubMed, LILACS, CAPES periodical, Open Journal System. Os descritores usados foram: "toxidade crônica ao etanol", "toxidade crônica ao álcool", "toxicidade aguda ao etanol", "toxicidade aguda ao álcool", "desenvolvimento ontogênico neural", "distúrbios da migração neuronal", "estrutura neural".Foram considerados critérios de inclusão: artigos publicados no periódo de 2003 e 2007, alguns artigos clássicos da área, e um livro básico em neuropsicologia. RESULTADOS constatou-se que muitos estudos sobre os efeitos crônicos do etanol sobre o sistema neural de mamíferos foram feitos, mas poucos estudos foram realizados sobre os efeitos agudos do etanol em dias específicos da gestação, e esses revelaram importantes desordens sobre o tecido neural. CONCLUSÕES: o consumo de etanol não é recomendado para mulheres na fase gestacional para preservar a saúde do feto, e o consumo agudo de etanol entre mulheres próxima à oitava e nona semanas de gestação têm demonstrado ser potencialmente perigoso para o tecido neural do feto.