An animal model for mania: Preliminary results

El‐Mallakh, Rif S.; Harrison, Linda T.; Li, Rena; Changaris, David G.; Levy, Robert S.

doi:10.1016/0278-5846(95)00123-d

Cited by 75 publications

(32 citation statements)

References 15 publications

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“…Since the rearing behavior is correlated with manic-like behaviors, 54, 55 we measured a number of episodes of standing on the two hind limbs for more than 5 s (Figure 2b). The change in the frequency of rearing behavior from pre-kindling to kindling and post-kindling showed significant main effect of kindling (F 1,20 =12.15, P =0.002), sex (F 1,20 =9.74, P =0.005), but not interaction (F 1,20 =1.86, P =0.18).…”

Section: Resultsmentioning

confidence: 99%

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Sex differences in mania phenotype and ethanol consumption in the lateral hypothalamic kindled rat model

et al. 2015

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Sex differences have been observed in mania phenotypes in humans. However the mechanisms underlying this difference are poorly understood. Activating the lateral hypothalamus is implicated in manic-like behaviors in rodents. Using newly established lateral hypothalamus kindled (LHK) rat mania model, we investigated sex differences of manic-like behaviors and its correlation with voluntary ethanol intake. We stimulated the lateral hypothalamus bilaterally in the male and female Wistar rats over five consecutive days. We recorded and quantified kindling-induced behaviors for each individual animal. We also assessed ethanol consumption using a two-bottle choice ethanol drinking as well as circadian locomotor activity counts daily throughout the experiment. We found notable sex differences in several aspects of manic-like behaviors during kindling. Males exhibited a significantly increased locomotor activity during the light phase, and reduced rest interval. On the other hand, females displayed significantly higher ethanol consumption and more frequent rearing behavior. However, no sex differences were present in the duration of sexual, feeding or grooming behaviors or in dark-phase activity counts. The excessive alcohol intake in LHK female rats is reminiscent of clinically reported sex differences in bipolar patients while the other phenotypic sex differences such as rearing and locomotor activity are less clearly described in clinical studies. Overall, our results lend further evidence for the validity of the LHK rat as a useful model to study brain region-specific molecular changes during mania and its correlation with alcohol use disorders.

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Section: Resultsmentioning

confidence: 99%

“…60 Change in rearing frequency has been considered a measure for manic-like behavior in animal models. 54, 55 Female Wistar rats generally display more rearing activity than males at baseline. 61 To correct for this baseline difference, we compared the changes in rearing frequency rather than actual frequency between males and females.…”

Section: Discussionmentioning

confidence: 96%

Sex differences in mania phenotype and ethanol consumption in the lateral hypothalamic kindled rat model

et al. 2015

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“…Acute intracerebroventricular administration of 5 μ l of 1 mM ouabain solution in rats produced a “mania-like hyperactivation” of the animals studied with automated activity monitors (el-Mallakh et al, 1995). Later, the same group reported that persistent hyperreactivity induced by central administration of ouabain was associated with substantial increases in ouabain binding and Na + /K + -ATPase activity in the hippocampus (Ruktanonchai et al, 1998).…”

Section: Other Conditionsmentioning

confidence: 99%

Endogenous Cardiotonic Steroids: Physiology, Pharmacology, and Novel Therapeutic Targets

Shapiro²,

2009

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“…The adenosine triphosphotase inhibitor, ouabain, administered ICV also induces hyperactivity in the open field and this treatment has been proposed as a model of mania (el-Mallakh et al, 1995) (Table 2). Moreover, this effect can last for seven days after a single ICV infusion (Riegel et al, 2009).…”

Section: Pharmacological Models Of Maniamentioning

confidence: 99%

Animal models of bipolar mania: The past, present and future

2016

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Bipolar disorder (BD) is the sixth leading cause of disability in the world according to the World Health Organization and affects nearly 6 million (~2.5% of the population) adults in the United State alone each year. BD is primarily characterized by mood cycling of depressive (e.g., helplessness, reduced energy and activity, and anhedonia) and manic (e.g., increased energy and hyperactivity, reduced need for sleep, impulsivity, reduced anxiety and depression), episodes. The following review describes several animal models of bipolar mania with a focus on more recent findings using genetically modified mice, including several with the potential of investigating the mechanisms underlying ‘mood’ cycling (or behavioral switching in rodents). We discuss whether each of these models satisfy criteria of validity (i.e., face, predictive, and construct), while highlighting their strengths and limitations. Animal models are helping to address critical questions related to pathophysiology of bipolar mania, in an effort to more clearly define necessary targets of first-line medications, lithium and valproic acid, and to discover novel mechanisms with the hope of developing more effective therapeutics. Future studies will leverage new technologies and strategies for integrating animal and human data to reveal important insights into the etiology, pathophysiology, and treatment of BD.

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An animal model for mania: Preliminary results

Cited by 75 publications

References 15 publications

Sex differences in mania phenotype and ethanol consumption in the lateral hypothalamic kindled rat model

Sex differences in mania phenotype and ethanol consumption in the lateral hypothalamic kindled rat model

Endogenous Cardiotonic Steroids: Physiology, Pharmacology, and Novel Therapeutic Targets

Animal models of bipolar mania: The past, present and future

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