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oai:riuma.uma.es:10630/331592026-02-03T10:49:05Zcom_10630_2254col_10630_37953

00925njm 22002777a 4500 dc Blanco-Calvo, Eduardo author Campos-Sandoval, José Ángel author Palomino, Ana author Luque-Rojas, María Jesús author Bilbao, Ainhoa author Suárez, Juan author Márquez-Gómez, Javier author Rodriguez-de-Fonseca, Fernando author 2012 Glutaminase is considered the main Glutamate (Glu) producing enzyme. Two isoforms, liver (LGA) and kidney (KGA) type glutaminases have been identified in neurons. The role of both enzymes in psychopharmacological responses to cocaine remains unknown. We examined both mRNA and protein expression of KGA and LGA in the brain of mice sensitized to cocaine. Additionally, total glutaminase activity was also measured. Total glutaminase activity and mRNA and protein expression of KGA and LGA were measured on the dorsal striatum, prefrontal cortex, hippocampus and cerebellum of cocaine-sensitized mice. Cocaine-sensitized animals (20 mg/kg x 5 days, followed of 5 drug-free days) exhibited a decrease of total glutaminase activity in both the dorsal striatum and the prefrontal cortex. This was associated with an increase in KGA mRNA expression in both brain areas,that was not observed when protein KGA levels were measured by western blot. LGA mRNA expression was increased as results of acute cocaine administration in sensitized animals, although protein levels were only enhanced in the prefrontal cortex of sensitized mice. These findings suggest that chronic cocaine administration modulates glutamate production through the regulation of glutaminase expression and activity. These actions are mainly observed in the prefrontal cortexdorsal striatum circuit, the neuroanatomical target for the psychostimulant sensitization properties of cocaine. Blanco, E., Campos-Sandoval, J.Á., Palomino, A. et al. Cocaine modulates both glutaminase gene expression and glutaminase activity in the brain of cocaine-sensitized mice. Psychopharmacology 219, 933–944 (2012). https://doi.org/10.1007/s00213-011-2418-x https://hdl.handle.net/10630/33159 10.1007/s00213-011-2418-x Expresión génica Regulación genética Cocaine modulates both glutaminase gene expression and glutaminase activity in the brain of cocaine-sensitized mice