Several works report brain impairment of metabolism as a mechanism underlying depression.
Citrate synthase and
succinate dehydrogenase are
enzymes localized within cells in the mitochondrial matrix and are important steps of Krebs cycle. In addition,
citrate synthase has been used as a quantitative
enzyme marker for the presence of intact mitochondria. Thus, we investigated
citrate synthase and
succinate dehydrogenase activities from rat brain after chronic administration of
paroxetine, nortriptiline and
venlafaxine. Adult male Wistar rats received daily
injections of
paroxetine (10mg/kg), nortriptiline (15mg/kg),
venlafaxine (10mg/kg) or saline in 1.0mL/kg volume for 15 days. Twelve hours after the last administration, the rats were killed by
decapitation, the hippocampus, striatum and prefrontal cortex were immediately removed, and activities of
citrate synthase and
succinate dehydrogenase were measured. We verified that chronic administration of
paroxetine increased
citrate synthase activity in the prefrontal cortex, hippocampus, striatum and cerebral cortex of adult rats; cerebellum was not affected. Chronic administration of nortriptiline and
venlafaxine did not affect the
enzyme activity in these brain areas.
Succinate dehydrogenase activity was increased by chronic administration of
paroxetine and nortriptiline in the prefrontal cortex, hippocampus, striatum and cerebral cortex of adult rats; cerebellum was not affected either. Chronic administration of
venlafaxine increased
succinate dehydrogenase activity in prefrontal cortex, but did not affect the
enzyme activity in cerebellum, hippocampus, striatum and cerebral cortex. Considering that metabolism impairment is probably involved in the pathophysiology of
depressive disorders, an increase in these
enzymes by
antidepressants may be an important mechanism of action of these drugs.