title: Brain creatine kinase activity is increased by chronic administration of paroxetine.
abstract: 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.
authors.affiliation: Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Santos
authors.forename: Giselli
authors.initials: G
authors.lastname: Scaini
authors.forename: Gislaine T
authors.initials: GT
authors.lastname: Rezin
authors.forename: Joana
authors.initials: J
authors.lastname: Benedet
authors.forename: Natália
authors.initials: N
authors.lastname: Rochi
authors.forename: Gabriela C
authors.initials: GC
authors.lastname: Jeremias
authors.forename: Milena
authors.initials: M
authors.lastname: Carvalho-Silva
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Streck
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D052276:Creatine Kinase, BB Form / Q000378:metabolism*; D003511:Cyclohexanols / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009661:Nortriptyline / Q000494:pharmacology; D017374:Paroxetine / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D000069470:Venlafaxine Hydrochloride
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D052276:Creatine Kinase, BB Form; D003511:Cyclohexanols; D009661:Nortriptyline; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride