Open field is more sensitive than automated activity monitor in documenting ouabain-induced hyperlocomotion in the development of an animal model for bipolar illness

Decker, Sarah; Grider, Glenna; Cobb, Mahoney; Li, Xiaoping; Huff, Mary O.; El‐Mallakh, Rif S.; Levy, Robert S.

doi:10.1016/s0278-5846(99)00111-6

Cited by 53 publications

(34 citation statements)

References 10 publications

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“…Since the present study was the first direct exploration of the affective-like behavioral effects of PKC inhibition, care was taken in the design of the study to increase the likelihood of therapeutically meaningful results: (1) the use of more than one model and of two amphetamine treatment schedules, acute and sensitized responses [20,53] ; (2) the use of a large open field rather than standard activity monitors (testing in a large environment has been demonstrated to be more sensitive to behavioral change [38] ); (3) the use of a continuous, automated data collection system to reduce inaccuracies related to sampling or human errors, and (4) data analysis methods were chosen in order to correct for multiple comparisons in the open field statistics. Considering the careful design and the changes in distinct behaviors, the data suggest that acute tamoxifen treatment is able to reduce manic-like behaviors in rats.…”

Section: Discussionmentioning

confidence: 99%

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Protein Kinase C Inhibition by Tamoxifen Antagonizes Manic-Like Behavior in Rats: Implications for the Development of Novel Therapeutics for Bipolar Disorder

et al. 2007

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Rationale: In the context of bipolar disorder (BPD) research it was demonstrated that administration of the structurally dissimilar mood stabilizers lithium and valproate produced a striking reduction in protein kinase C (PKC) in rat brain. In a small clinical study, tamoxifen (a PKC inhibitor) had antimanic efficacy. However, both lithium and valproate exert many biochemical changes and attribution of therapeutic relevance to any molecular findings needs to be based on linking them to behavioral effects. Objectives: The present study was designed to explore such relationship by studying the effects of PKC inhibition in amphetamine-induced behavioral animal models of mania and changes in GAP-43. Methods: The effects of two daily tamoxifen (1 mg/kg) i.p. injections on acute or chronic (7 injections) amphetamine (0.5 mg/kg) -induced behaviors and GAP-43 phosphorylation were tested. Results: The study demonstrates that tamoxifen significantly reduced amphetamine-induced hyperactivity in a large open field without affecting spontaneous activity levels and normalized amphetamine-induced increase in visits to the center of an open field (representing risk-taking behavior). Tamoxifen also attenuated amphetamine-induced phosphorylation of GAP-43, a result that is consistent with the behavioral findings. Conclusions: These results support the possibility that PKC signaling may play an important role in the pathophysiology and treatment of BPD. These findings may have direct clinical implications as they offer a new avenue for attempts to develop more specific drugs for the disorder.

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Section: Discussionmentioning

confidence: 99%

“…120 cm transparent Plexiglas platform without walls, elevated 80 cm above the floor) served to study locomotor and exploratory behavior. Such large open fields were previously demonstrated to be much more effective in the study of behavior compared with the commonly used smaller activity monitors [38] . A center square of 40 !…”

Section: Equipmentmentioning

confidence: 99%

Protein Kinase C Inhibition by Tamoxifen Antagonizes Manic-Like Behavior in Rats: Implications for the Development of Novel Therapeutics for Bipolar Disorder

et al. 2007

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“…One facet of mania that is heavily modeled is hyperactivity as currently most models of mania focus only on this component of the behavior (Decker et al 2000;Einat et al 2000;Post and Weiss 1989;Ralph-Williams et al 2003;Shaldivin et al 2001;Shaldubina et al 2002). The most commonly used model is psychostimulant-induced hyperactivity and whereas this model has partial validity it also has a lot of limitations (Einat et al in press).…”

Section: Psychostimulants-induced Hyperactivitymentioning

confidence: 99%

“…These variations are more prominent during chronic psychostimulant treatment but are also apparent after acute administration (Einat et al 1996). For example, hyperactivity measures had been shown to increase more in large open field arena compared to smaller activity monitors (Decker et al 2000) and an environment that is similar to the home cage had been demonstrated to hinder the development of ambulatory activity (Cabib 1993;Einat and Szechtman 1993).…”

Section: Psychostimulants-induced Hyperactivitymentioning

confidence: 99%

Establishment of a Battery of Simple Models for Facets of Bipolar Disorder: A Practical Approach to Achieve Increased Validity, Better Screening and Possible Insights into Endophenotypes of Disease

Einat

2006

Behav Genet

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The lack of appropriate animal models for bipolar disorder (BPD) hinders the translation of novel molecular and genetic findings into the development of new more efficient treatments. Attempts to develop a comprehensive model for BPD did not result in a practical and valid model and at present most studies utilize a limited number of models for specific components of the disorder. Whereas there is a higher availability of models for the depression pole of BPD, only a few models represent the manic pole with the most frequently used being psychostimulant-induced hyperactivity. This last model had been important in studies of the disease and has some validity but it is clear that by itself cannot be considered to represent mania. Additional models for facets of BPD are needed to allow better screening of new drugs and new mutant mice. Such models may also support the exploration of endophenotypes of BPD and the mechanisms of the disease. An advantage of a battery approach is that each model can be only partially valid when used alone but the combination of a few models may result in strong validity. The present study suggests that such a battery can be based on existing models previously developed in the context of studying normal behavior or other disorders after an initial validation in the context of BPD. An example for this idea is described using the resident-intruder test for aggression. Present results show that 3 weeks oral treatment with 1.2-2.4% lithium (increasing doses), or 20 g/kg daily dose of valproate, significantly reduced aggressive behavior in resident mice without affecting non-aggressive social interactions. Accordingly, it is suggested that the simplified resident-intruder paradigm may model the aggression related to mania as part of a test battery for facets of BPD. It is further speculated that, pending further research, this paradigm can be combined with additional methods to explore changes in the LHPA axis that may be linked to an important endophenotype of BPD.

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“…It is known that the intracerebroventricular (ICV) injection of ouabain (OUA), a potent Na/K ATPase pump inhibitor, induces hyperlocomotion 22,23 , which may persist for several days a er a single injection 24 . us, the present study aims to investigate the e ects of ICV administration of OUA in rats on BDNF expression in the hippocampus and amygdala immediately, 1h, or 24h, to mimic an acute episode of mania, and seven days, to mimic the persistence of a manic episode, a er ouabain injection.…”

Section: Introductionmentioning

confidence: 99%

Decreased BDNF levels in amygdala and hippocampus after intracerebroventricular administration of ouabain

Jornada

Valvassori

Resende

et al. 2012

Rev. psiquiatr. clín.

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Objective: e present study aims to investigate the e ects of ouabain intracerebroventricular injection on BDNF levels in the amygdala and hippocampus of Wistar rats. Methods: Animals received a single intracerebroventricular injection of ouabain (10 -3 and 10 -2 M) or arti cial cerebrospinal uid and immediately, 1h, 24h, or seven days a er injection, BDNF levels were measured in the rat's amygdala and hippocampus by sandwich-ELISA (n = 8 animals per group). Results: When evaluated immediately, 3h, or 24h a er injection, ouabain in doses of 10 -2 and 10 -3 M does not alter BDNF levels in the amygdala and hippocampus. However, when evaluated seven days a er injection, ouabain in 10 -2 and 10 -3 M, showed a signi cant reduction in BDNF levels in both brain regions evaluated. Discussion: In conclusion, we propose that the ouabain decreased BDNF levels in the hippocampus and amygdala when assessed seven days a er administration, supporting the Na/K ATPase hypothesis for bipolar illness. ResumoObjetivo: O presente estudo tem como objetivo investigar os efeitos da injeção intracerebroventricular de ouabaína sobre os níveis de BDNF na amígdala e no hipocampo de ratos Wistar. Métodos: Os animais receberam uma única injeção intracerebroventricular de ouabaína (10 -3 and 10 -2 M) ou uido cerebroespinhal arti cial e, imediatamente, 3h, 24h ou sete dias após a injeção, os níveis de BDNF foram mensurados na amígdala e hipocampo dos ratos por ELISA sandwich (n = 8 animais por grupo). Resultados: Quando avaliados imediatamente após a injeção, 3h ou 24h, ouabaína nas doses 10 -2 e 10 -3 M não alterou os níveis de BDNF em ambas as estruturas avaliadas. Entretanto, quando avaliados sete dias após a injeção, ouabaína nas doses 10 -2 e 10 -3 M mostrou uma signi cante redução nos níveis de BDNF em amígdala e hipocampo. Conclusão: Em conclusão, propõe-se que a administração de ouabaína diminuiu os níveis de BDNF em amígdala e hipocampo quando avaliados sete dias após a injeção, suportando a hipótese da participação da Na/K ATPase no transtorno bipolar. Jornada LK, et al. / Rev Psiq Clín. 2012;39(5):157-60 Palavras-chave: BDNF, mania, Na/K ATPase, ouabaína.

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Open field is more sensitive than automated activity monitor in documenting ouabain-induced hyperlocomotion in the development of an animal model for bipolar illness

Cited by 53 publications

References 10 publications

Protein Kinase C Inhibition by Tamoxifen Antagonizes Manic-Like Behavior in Rats: Implications for the Development of Novel Therapeutics for Bipolar Disorder

Protein Kinase C Inhibition by Tamoxifen Antagonizes Manic-Like Behavior in Rats: Implications for the Development of Novel Therapeutics for Bipolar Disorder

Establishment of a Battery of Simple Models for Facets of Bipolar Disorder: A Practical Approach to Achieve Increased Validity, Better Screening and Possible Insights into Endophenotypes of Disease

Decreased BDNF levels in amygdala and hippocampus after intracerebroventricular administration of ouabain

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