Schizophrenia & Mania – Amphetamine/CDP-Induced Hyperactivity
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This test has predictive validity for Mania and Manic phase of the bipolar disorder. Models for mania are scarce and hyperactivity-based studies are often used to mimic the mania/psychosis associated with bipolar disorder.
Combination of amphetamine and chlordiazepoxide (CDP) produce an increase in locomotor activity in C57Bl/6J mice that is higher in magnitude than amphetamine alone -induced activity. Agents used to treat bipolar disorder in humans, such as valproate (400 mg/kg, i.p) selectively attenuate this amphetamine/CDP-induced hyperactivity in mice without affecting locomotor activity induced by amphetamine alone.
Anti-manic compounds in prepulse inhibition of the startle response (PPI)
Administration of valproate (400 mg/kg, i.p.), lamotrigine (27 mg/kg, i.p.), or lithium chloride (2 mEq/kg) increases prepulse inhibition in C57Bl/6J mice. Therefore, this test can be used to screen potential therapeutic compounds for the treatment of bipolar disorder.
Anti-manic compounds in PPI 8
As noted above, pre-pulse inhibition is enhanced by the administration of antipsychotic medications such as clozapine or haloperidol. Similarly, administration of valproate, lithium or lamotrigine enhances PPI in mice. Therefore, PPI provides a preclinical screen for potential therapeutic compounds for the treatment of bipolar disorder.
