Tamoxifen effects on respiratory chain complexes and creatine kinase activities in an animal model of mania

Abstract

The present study aimed to investigate the effects of tamoxifen (TMX) on locomotor behavior and on the activities of mitochondrial respiratory chain complexes and creatine kinase (CK) in the brain of rats subjected to an animal model of mania induced by d-amphetamine (D-AMPH)-reversion and prevention protocols. The D-AMPH administration increased locomotor activity in saline-treated rats under prevention and reversion treatment; furthermore, there was evident reduction in the locomotion in the D-amphetamine group treated with TMX. D-AMPH significantly decreased the activity of mitochondrial respiratory chain complexes in saline-treated rats in prefrontal cortex, hippocampus, striatum and amygdala in both prevention and reversion treatment. Depending on the cerebral area and evaluated complex, TMX was able to prevent and reverse this impairment. A decrease in CK activity was also verified in the brain of rats when D-AMPH was administrated in both experiments; the administration of TMX reversed but not prevented the decrease in CK activity induced by D-AMPH. The present study demonstrated that TMX reversed and prevented the alterations in behavioral and energy metabolism induced by D-AMPH (alterations were also observed in bipolar disorder), reinforcing the need for more studies about inhibitors of PKC as possible targets for new medications in the treatment of bipolar disorder.

Behavioral and neurochemical effects of sodium butyrate in an animal model of mania

“…Mitochondria are important in adenosine 5 0 -triphosphate production through oxidative phosphorylation, a process carried out by the respiratory chain complexes I, II, III, and V. Our results showed that administration of d-AMPH resulted in an inhibition of mitochondrial respiratory-chain complexes I, II, II-III, and IV in the prefrontal cortex, hippocampus, striatum, and amygdala, confirming previous studies that reported a decrease in mitochondrial function during mania (Andreazza et al, 2010;Valvassori et al, 2010;Moretti et al, 2011).…”

A gene co-expression module implicating the mitochondrial electron transport chain is associated with long-term response to lithium treatment in bipolar affective disorder

“…This includes a number of the mitochondrially-encoded genes found to be altered in the present study such as MT-ND2 and MT-ATP6 among others. Secondly, in addition to evidence from gene expression studies, there are many other lines of evidence ranging from post-mortem, genetic, brain imaging, peripheral cell, and animal studies that point to general mitochondrial dysfunction in the pathophysiology of BPAD 50–52 . And thirdly, lithium treatment has been shown on multiple occasions to impact mitochondrial functioning, at least in part by modulating ETC and OXPHOS pathway activity 53,54 .…”

Comparing the effects of 17β-oestradiol and the selective oestrogen receptor modulators, raloxifene and tamoxifen, on prepulse inhibition in female rats

“…In another behavioural paradigm relevant to psychosis-like behaviours, tamoxifen treatment of intact male rats both reversed and prevented amphetamine-induced locomotion in the open-field test (Moretti et al, 2011;Steckert et al, 2012). A limited number of preclinical studies have investigated the effects of SERMs on cognitive function and mood.…”