Đang chuẩn bị liên kết để tải về tài liệu:
Caffeine and a selective adenosine A2A receptor antagonist induce sensitization and cross-sensitization behavior associated with increased striatal dopamine in mice

Caffeine, a nonselective adenosine A1 and A2A receptor antagonist, is the most widely used psychoactive substance in the world. Evidence demonstrates that caffeine and selective adenosine A2A antagonists interact with the neuronal systems involved in drug reinforcement, locomotor sensitization, and therapeutic effect in Parkinson's disease (PD). Evidence also indicates that low doses of caffeine and a selective adenosine A2A antagonist SCH58261 elicit locomotor stimulation whereas high doses of these drugs exert locomotor. | NSC Hsu et al. Journal of Biomedical Science 2010 17 4 http www.jbiomedsci.eom content 17 1 4 The cost of publication in Journal of Biomedical Science is bourne by the National Science Council Taiwan. JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Caffeine and a selective adenosine A2A receptor antagonist induce sensitization and cross-sensitization behavior associated with increased striatal dopamine in mice Chih W Hsu 1 2 Chin S Wang4 and Ted H Chiu 3 5 Abstract Background Caffeine a nonselective adenosine A1 and A2A receptor antagonist is the most widely used psychoactive substance in the world. Evidence demonstrates that caffeine and selective adenosine A2A antagonists interact with the neuronal systems involved in drug reinforcement locomotor sensitization and therapeutic effect in Parkinson s disease PD . Evidence also indicates that low doses of caffeine and a selective adenosine A2A antagonist SCH58261 elicit locomotor stimulation whereas high doses of these drugs exert locomotor inhibition. Since these behavioral and therapeutic effects are mediated by the mesolimbic and nigrostriatal dopaminergic pathways which project to the striatum we hypothesize that low doses of caffeine and SCH58261 may modulate the functions of dopaminergic neurons in the striatum. Methods In this study we evaluated the neuroadaptations in the striatum by using reverse-phase high performance liquid chromatography HPLC to quantitate the concentrations of striatal dopamine and its metabolites dihydroxylphenylacetic acid DOPAC and homovanilic acid HVA and using immunoblotting to measure the level of phosphorylation of tyrosine hydroxylase TH at Ser31 following chronic caffeine and SCH58261 sensitization in mice. Moreover to validate further that the behavior sensitization of caffeine is through antagonism at the adenosine A2A receptor we also evaluate whether chronic pretreatment with a selective adenosine A2A antagonist SCH58261 or a selective adenosine A1 antagonist DPCPX can .