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Effects of acute administration of mazindol on brain energy metabolism in adult mice

Published online by Cambridge University Press:  19 September 2013

Cinara Ludvig Gonçalves ,
Giselli Scaini ,
Gislaine Tezza Rezin ,
Isabela Casagrande Jeremias ,
Gisele Daiane Bez ,
Juliana Felipe Daufenbach ,
Lara Mezari Gomes ,
Gabriela Kozuchovski Ferreira ,
Alexandra Ioppi Zugno  and
Emilio Luiz Streck
Cinara Ludvig Gonçalves
Affiliation:
Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Porto Alegre, RS, Brazil Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Florianópolis, SC, Brazil
Giselli Scaini
Affiliation:
Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Porto Alegre, RS, Brazil Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Florianópolis, SC, Brazil
Gislaine Tezza Rezin
Affiliation:
Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Porto Alegre, RS, Brazil Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Florianópolis, SC, Brazil
Isabela Casagrande Jeremias
Affiliation:
Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Porto Alegre, RS, Brazil Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Florianópolis, SC, Brazil
Gisele Daiane Bez
Affiliation:
Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Porto Alegre, RS, Brazil Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Florianópolis, SC, Brazil
Juliana Felipe Daufenbach
Affiliation:
Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Porto Alegre, RS, Brazil Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Florianópolis, SC, Brazil
Lara Mezari Gomes
Affiliation:
Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Porto Alegre, RS, Brazil Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Florianópolis, SC, Brazil
Gabriela Kozuchovski Ferreira
Affiliation:
Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Porto Alegre, RS, Brazil Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Florianópolis, SC, Brazil
Alexandra Ioppi Zugno
Affiliation:
Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Porto Alegre, RS, Brazil Laboratório de Neurociências, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
Emilio Luiz Streck*
Affiliation:
Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Porto Alegre, RS, Brazil Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Florianópolis, SC, Brazil
*
Prof. Emilio L. Streck, Laboratório de Bioenergética, Universidade do Extremo Sul Catarinense, Av. Universitária, 1105, Criciúma, 88806-000 SC, Brazil. Tel: +55 48 3431 2539; Fax: +55 48 3431 2644; E-mail: [email protected]
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Abstract

Objectives

Mazindol is a sympathomimetic amine, widely used as an anorectic agent in the treatment of obesity. This drug causes psychostimulant effects because of its pharmacological profile similar to amphetamine, acting like a monoamine reuptake inhibitor. However, the mechanisms underlying the action of mazindol are still not clearly understood.

Methods

Swiss mice received a single acute administration of mazindol (0.25, 1.25 and 2.5 mg/kg, ip) or saline. After 2 h, the animals were killed by decapitation; the brain was removed and used for the evaluation of activities of mitochondrial respiratory chain complexes, Krebs cycle enzymes and creatine kinase.

Results

Acute administration of mazindol decreased complex I activity only in the hippocampus. Complex IV activity was increased in the cerebellum (2.5 mg/kg) and cerebral cortex (0.25 mg/kg). Citrate synthase activity was increased in the cerebellum (1.25 mg/kg) and cerebral cortex (1.25 mg/kg), and creatine kinase activity was increased in the cerebellum (1.25 mg/kg).

Conclusion

We suggest that the inhibition of complex I in the hippocampus only and activation of complex IV, citrate synthase and creatine kinase occurs because of a stimulus effect of mazindol in the central nervous system, which causes a direct impairment on energy metabolism.

Keywords

braincreatine kinasekrebs cyclemazindolmitochondrial respiratory chain
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 26 , Issue 3 , June 2014 , pp. 146 - 154
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2013 

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