Abstract:
:Bipolar disorder (BD) is a psychiatric disorder characterized by alternating episodes of mania and depression. The intracerebroventricular (i.c.v) administration of ouabain (a Na(+)/K(+)-ATPase inhibitor) in rats has been used as an animal model of mania, because present face, construct and predictive validities. Several studies strongly suggest that mitochondrial dysfunction play a central role in the pathophysiology of BD. Citrate synthase (CS) is an enzyme localized in the mitochondrial matrix and represents one of the most important steps of Krebs cycle. The aim of this study was to investigate CS activity in brain of rats after the administration of ouabain. Adult male Wistar rats received a single i.c.v. administration of ouabain (10(-2) and 10(-3) M) or vehicle (control group). Locomotor activity was measured using the open field task. CS activity was measured in the brain of rats immediately (1 h) and 7 days after ouabain administration. Our results showed that spontaneous locomotion was increased 1 h after ouabain administration, and that the hyperlocomotion persists 7 days after the administration. Moreover, CS activity was inhibited immediately after the administration of ouabain in the prefrontal cortex at the doses of 10(-3) and 10(-2) M. This inhibition remains by 7 days after the administration of ouabain. On the other hand, it was not observed any difference in CS activity in the hippocampus and striatum. Considering that inhibition of CS activity may reflect a mitochondrial dysfunction, it is tempting to speculate that the reduction of brain energy metabolism might be related to the pathophysiology of BD.
journal_name
Mol Cell Biochemjournal_title
Molecular and cellular biochemistryauthors
Freitas TP,Rezin GT,Gonçalves CL,Jeremias GC,Gomes LM,Scaini G,Teodorak BP,Valvassori SS,Quevedo J,Streck ELdoi
10.1007/s11010-010-0455-0subject
Has Abstractpub_date
2010-08-01 00:00:00pages
245-9issue
1-2eissn
0300-8177issn
1573-4919journal_volume
341pub_type
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