TY - JOUR T1 - Regulation of α-Synuclein Expression in Limbic and Motor Brain Regions of Morphine-Treated Mice JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4996 LP - 5003 DO - 10.1523/JNEUROSCI.4376-04.2005 VL - 25 IS - 20 AU - Barbara Ziolkowska AU - Agnieszka Gieryk AU - Wiktor Bilecki AU - Agnieszka Wawrzczak-Bargiela AU - Krzysztof Wedzony AU - Agnieszka Chocyk AU - Patria E. Danielson AU - Elizabeth A. Thomas AU - Brian S. Hilbush AU - J. Gregor Sutcliffe AU - Ryszard Przewlocki Y1 - 2005/05/18 UR - http://www.jneurosci.org/content/25/20/4996.abstract N2 - Chronic exposure to opiates produces dependence and addiction, which may result from neuroadaptations in the dopaminergic reward pathway and its target brain regions. The neuronal protein α-synuclein has been implicated in neuronal plasticity and proposed to serve as a negative regulator of dopamine neurotransmission. Thus, α-synuclein could mediate some effects of opiates in the brain. The present study investigated the influence of acute and chronic morphine administration on α-synuclein mRNA and protein expression in the brains of mice. Downregulation of α-synuclein mRNA was observed in the basolateral amygdala, dorsal striatum, nucleus accumbens, and ventral tegmental area of mice withdrawn from chronic morphine treatment. The changes were the most pronounced after longer periods of withdrawal (48 h). In contrast, levels of α-synuclein protein, as assessed by Western blotting, were significantly increased in the amygdala and striatum/accumbens (but not in the mesencephalon) of morphine-withdrawn mice. In both brain regions, levels of α-synuclein were elevated for as long as 2 weeks after treatment cessation. Because α-synuclein is a presynaptic protein, the detected opposite changes in its mRNA and protein levels are likely to take place in different populations of projection neurons whose somata are in different brain areas. Axonal localization of α-synuclein was confirmed by immunofluorescent labeling. An attempt to identify postsynaptic neurons innervated by α-synuclein-containing axon terminals revealed their selective apposition to calbindin D28K-negative projection neurons in the basolateral amygdala. The observed changes in α-synuclein levels are discussed in connection with their putative role in mediating suppression of dopaminergic neurotransmission during opiate withdrawal. ER -