Effect of acute administration of ketamine and imipramine on creatine kinase activity in the brain of rats

Assis, Lara C.; Rezin, Gislaine T.; Comim, Clarissa M.; Valvassori, Samira S.; Jeremias, Isabela C.; Zugno, Alexandra I.; Quevedo, Joao L De; Streck, Emílio L.

doi:10.1590/s1516-44462009000300010

Cited by 28 publications

(20 citation statements)

References 54 publications

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“…Moreover, in another study it was demonstrated that imipramine, antagonist NMDA receptor ketamine (Assis et al 2009) and antidepressant paroxetine (Santos et al 2009) increased creatine kinase activity in rat brain, suggesting that modulation of energy metabolism by antidepressants could be an important mechanism of action of these drugs. In fact, mitochondria seem to be a target for antidepressant drugs (Weinbach et al 1986).…”

Section: Discussionmentioning

confidence: 98%

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Administration of memantine and imipramine alters mitochondrial respiratory chain and creatine kinase activities in rat brain

et al. 2011

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Several studies have appointed for a role of glutamatergic system and/or mitochondrial function in major depression. In the present study, we evaluated the creatine kinase and mitochondrial respiratory chain activities after acute and chronic treatments with memantine (N-methyl-D: -aspartate receptor antagonist) and imipramine (tricyclic antidepressant) in rats. To this aim, rats were acutely or chronically treated for 14 days once a day with saline, memantine (5, 10 and 20 mg/kg) and imipramine (10, 20 and 30 mg/kg). After acute or chronic treatments, we evaluated mitochondrial respiratory chain complexes (I, II, II-III and IV) and creatine kinase activities in prefrontal cortex, hippocampus and striatum. Our results showed that both acute and chronic treatments with memantine or imipramine altered respiratory chain complexes and creatine kinase activities in rat brain; however, these alterations were different with relation to protocols (acute or chronic), complex, dose and brain area. Finally, these findings further support the hypothesis that the effects of imipramine and memantine could be involve mitochondrial function modulation.

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Section: Discussionmentioning

confidence: 98%

“…The creatine kinase activity has been implicated in the pathogenesis of a number of diseases, particularly in the brain (Assis et al 2009). Creatine kinase is an important enzyme responsible for normal energy homeostasis performing several integrated functions, such as, temporary Imipramine 20…”

Section: Discussionmentioning

confidence: 99%

Administration of memantine and imipramine alters mitochondrial respiratory chain and creatine kinase activities in rat brain

et al. 2011

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“…The NMDAR antagonist ketamine has been shown to elicit a rapid antidepressant action in preclinical and clinical reports (Autry et al 2011;Berman et al 2000;Li et al 2011). Interestingly, a study by Assis et al (2009) showed that the acute administration of ketamine, besides producing an anti-immobility effect, increased the creatine kinase activity in striatum, cerebral cortex and cerebellum. Memantine, another NMDAR antagonist with anti-immobility effect, also increased creatine kinase activity in prefrontal cortex and hippocampus of rats (Reus et al 2012).…”

Section: Discussionmentioning

confidence: 99%

“…A growing number of reports have provided evidence for the importance of the creatine kinase/phosphocreatine system in the pathophysiology of depression: (1) brain phosphocreatine, detected by phosphorus-31 magnetic resonance spectroscopy, was shown to be decreased in severely depressed patients (Kato et al 1992); (2) an inverse correlation between Hamilton Depression Rating Scale scores and white matter creatine levels was shown (Dager et al 2004); (3) single prolonged stress and forced swimming stress decreased creatine concentrations in the rat prefrontal cortex (Herring et al 2008;Kim et al 2010;Knox et al 2010); (4) learned helplessness, a well-validated animal model of depression, decreased the expression of hippocampal creatine transporter (Lugenbiel et al 2010); (5) the acute administration of the fast-acting antidepressant ketamine increased creatine kinase activity in rats (Assis et al 2009); (6) clinical trials show that creatine augmentation in antidepressant treatment-resistant patients may be a promising therapeutic approach that exhibits more rapid and efficacious responses (Kondo et al 2011;Lyoo et al 2012); (7) creatine administration in mice produced an anti-immobility effect in the tail suspension test (TST) and forced swimming test (FST), two widely used tests for screening antidepressants (Allen et al 2010, 2013a.…”

Section: Introductionmentioning

confidence: 99%

The modulation of NMDA receptors and l-arginine/nitric oxide pathway is implicated in the anti-immobility effect of creatine in the tail suspension test

et al. 2015

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The modulation of N-methyl-D-aspartate receptor (NMDAR) and L-arginine/nitric oxide (NO) pathway is a therapeutic strategy for treating depression and neurologic disorders that involves excitotoxicity. Literature data have reported that creatine exhibits antidepressant and neuroprotective effects, but the implication of NMDAR and L-arginine/nitric oxide (NO) pathway in these effects is not established. This study evaluated the influence of pharmacological agents that modulate NMDAR/L-arginine-NO pathway in the anti-immobility effect of creatine in the tail suspension test (TST) in mice. The NOx levels and cellular viability in hippocampal and cerebrocortical slices of creatine-treated mice were also evaluated. The anti-immobility effect of creatine (10 mg/kg, po) in the TST was abolished by NMDA (0.1 pmol/mouse, icv), D-serine (30 µg/mouse, icv, glycine-site NMDAR agonist), arcaine (1 mg/kg, ip, polyamine site NMDAR antagonist), L-arginine (750 mg/kg, ip, NO precursor), SNAP (25 μg/mouse, icv, NO donor), L-NAME (175 mg/kg, ip, non-selective NOS inhibitor) or 7-nitroindazole (50 mg/kg, ip, neuronal NOS inhibitor), but not by DNQX (2.5 µg/mouse, icv, AMPA receptor antagonist). The combined administration of sub-effective doses of creatine (0.01 mg/kg, po) and NMDAR antagonists MK-801 (0.001 mg/kg, po) or ketamine (0.1 mg/kg, ip) reduced immobility time in the TST. Creatine (10 mg/kg, po) increased cellular viability in hippocampal and cerebrocortical slices and enhanced hippocampal and cerebrocortical NO x levels, an effect potentiated by L-arginine or SNAP and abolished by 7-nitroindazole or L-NAME. In conclusion, the anti-immobility effect of creatine in the TST involves NMDAR inhibition and enhancement of NO levels accompanied by an increase in neural viability.

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“…In this context, a study conducted by Assis et al [12] showed that the acute ketamine administration produced an antidepressant-like effect that was associated with increased creatine kinase activity in striatum, cerebral cortex, and cerebellum. The creatine kinase/phosphocreatine system is a rapid alternative source for ATP synthesis in the brain, controlling neural energy demands [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Creatine, similarly to ketamine, affords antidepressant-like effects in the tail suspension test via adenosine A1 and A2A receptor activation

Cunha

Pazini

Rosa

et al. 2015

Purinergic Signalling

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The benefits of creatine supplementation have been reported in a broad range of central nervous systems diseases, including depression. A previous study from our group demonstrated that creatine produces an antidepressant-like effect in the tail suspension test (TST), a predictive model of antidepressant activity. Since depression is associated with a dysfunction of the adenosinergic system, we investigated the involvement of adenosine A 1 and A 2A receptors in the antidepressant-like effect of creatine in the TST. The anti-immobility effect of creatine (1 mg/kg, po) or ketamine (a fast-acting antidepressant, 1 mg/kg, ip) in the TST was prevented by pretreatment of mice with caffeine (3 mg/kg, ip, nonselective adenosine receptor antagonist), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) (2 mg/kg, ip, selective adenosine A 1 receptor antagonist), and 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-ylamino]ethyl)-phenol (ZM241385) (1 mg/kg, ip, selective adenosine A 2A receptor antagonist). In addition, the combined administration of subeffective doses of creatine and adenosine (0.1 mg/kg, ip, nonselective adenosine receptor agonist) or inosine (0.1 mg/kg, ip, nucleoside formed by the breakdown of adenosine) reduced immobility time in the TST. Moreover, the administration of subeffective doses of creatine or ketamine combined with N-6-cyclohexyladenosine (CHA) (0.05 mg/kg, ip, selective adenosine A 1 receptor agonist), N-6-[2-(3,5-dimethoxyphenyl)-2-(methylphenyl)ethyl]adenosine (DPMA) (0.1 mg/kg, ip, selective adenosine A 2A receptor agonist), or dipyridamole (0.1 μg/mouse, icv, adenosine transporter inhibitor) produced a synergistic antidepressant-like effect in the TST. These results indicate that creatine, similarly to ketamine, exhibits antidepressant-like effect in the TST probably mediated by the activation of both adenosine A 1 and A 2A receptors, further reinforcing the potential of targeting the purinergic system to the management of mood disorders.

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Effect of acute administration of ketamine and imipramine on creatine kinase activity in the brain of rats

Cited by 28 publications

References 54 publications

Administration of memantine and imipramine alters mitochondrial respiratory chain and creatine kinase activities in rat brain

Administration of memantine and imipramine alters mitochondrial respiratory chain and creatine kinase activities in rat brain

The modulation of NMDA receptors and l-arginine/nitric oxide pathway is implicated in the anti-immobility effect of creatine in the tail suspension test

Creatine, similarly to ketamine, affords antidepressant-like effects in the tail suspension test via adenosine A1 and A2A receptor activation

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