Major depression is a serious and recurrent disorder often manifested with symptoms at the psychological, behavioral, and physiological levels. In addition, several works also suggest brain metabolism impairment as a mechanism underlying depression.
Creatine kinase (CK) plays a central role in the metabolism of high-energy consuming tissues such as brain, where it functions as an effective buffering system of cellular
ATP levels. Considering that CK plays an important role in brain energy homeostasis and that some
antidepressants may modulate energy metabolism, we decided to investigate CK activity from rat brain after chronic administration of
paroxetine (
selective serotonin reuptake inhibitor), nortriptiline (
tricyclic antidepressant) and
venlafaxine (selective
serotonin-
norepinephrine reuptake inhibitor). Adult male Wistar rats received daily
injections of
paroxetine (10 mg/kg), nortriptiline (15 mg/kg),
venlafaxine (10 mg/kg) or saline in 1.0 mL/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 activity of CK was measured. Our results demonstrated that chronic administration of
paroxetine increased CK activity in the prefrontal cortex, hippocampus and striatum of adult rats. On the other hand, nortriptiline and
venlafaxine chronic administration did not affect CK activity in these brain areas. In order to verify whether the effect of
paroxetine on CK is direct or indirect, we also measured the in vitro effect of this drug on the activity of the
enzyme. We verified that
paroxetine did not affect CK activity in vitro. Considering that metabolism impairment is probably involved in the pathophysiology of
depressive disorders, an increase in CK activity by
antidepressants may be an important mechanism of action of these drugs.