Brain creatine kinase activity in an animal model of mania.
There is evidence pointing to dysfunction at the mitochondrial level as an important target for the understanding of the pathophysiology of bipolar disorder (BD). We assessed creatine kinase (CK) activity in rats submitted to an animal model of mania which included the use of lithium and valproate. In the acute treatment, amphetamine (AMPH) or saline was administered to rats for 14 days, and between day 8 and 14, rats were treated with either lithium, valproate or saline. In the maintenance treatment, rats were pretreated with lithium, valproate or saline, and between day 8 and 14, AMPH or saline were administered. In both experiments, locomotor activity was assessed by open-field test and CK activity was evaluated in hippocampus, striatum, cerebellum, whole cortex and prefrontal cortex. Our results showed that mood stabilizers reversed AMPH-induced behavioral effects. Moreover, AMPH (acute treatment) inhibited CK activity in hippocampus, striatum and cortex, but not in cerebellum and prefrontal cortex, and administration of lithium or valproate did not reverse the enzyme inhibition. In the maintenance treatment, AMPH decreased CK activity in saline-pretreated rats in hippocampus, striatum and cortex, but not in cerebellum and prefrontal cortex. AMPH administration in lithium- or valproate-pretreated animals decreased CK activity in hippocampus, striatum and cortex. Our results showed that AMPH inhibited CK activity and that mood stabilizers were not able to reverse and/or prevent the enzyme inhibition. These findings reinforce the hypothesis that mitochondrial dysfunction plays an important role in the pathophysiology of BD.
Streck
Emilio L
EL
Laboratório de Fisiopatologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil. emiliostreck@terra.com.br
Amboni
Graziela
G
Scaini
Giselli
G
Di-Pietro
Priscila B
PB
Rezin
Gislaine T
GT
Valvassori
Samira S
SS
Luz
Gabrielle
G
Kapczinski
Flávio
F
Quevedo
João
J
D000661:Amphetamine / Q000633:toxicity; D000818:Animals; D018692:Antimanic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D000697:Central Nervous System Stimulants / Q000633:toxicity; D003402:Creatine Kinase / Q000378:metabolism*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D007274:Injections, Intraperitoneal; D018020:Lithium Compounds / Q000627:therapeutic use; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014635:Valproic Acid / Q000627:therapeutic use
D018692:Antimanic Agents; D000697:Central Nervous System Stimulants; D018020:Lithium Compounds; D014635:Valproic Acid; D000661:Amphetamine; D003402:Creatine Kinase