Mood stabilizers increase prepulse inhibition in DBA/2NCrl mice

Area of Science:

• Neuroscience
• Pharmacology
• Psychiatry

Background:

• Mood stabilizers like lithium and antiepileptic drugs are used for bipolar disorder and schizophrenia.
• These psychiatric disorders are associated with deficits in prepulse inhibition (PPI) of the acoustic startle response.

Purpose of the Study:

• To investigate the efficacy of five clinically used mood stabilizers in the DBA/2 mouse model, which exhibits naturally low PPI.
• To determine if these mood stabilizers can increase PPI in this established animal model.

Main Methods:

• The DBA/2 mouse model was utilized to assess PPI.
• Five mood stabilizers (lithium chloride, topiramate, carbamazepine, valproic acid, lamotrigine) were administered intraperitoneally 30 minutes before testing.
• Dose-dependent effects on PPI, no-stimulus amplitudes, and startle amplitudes were analyzed.

Main Results:

• Lithium, topiramate, carbamazepine, valproic acid, and lamotrigine all demonstrated an increase in percent PPI.
• High doses of carbamazepine, valproic acid, and lamotrigine decreased no-stimulus amplitudes and increased startle amplitudes.
• The observed increases in PPI at high doses of these antiepileptic drugs were independent of startle amplitude changes.

Conclusions:

• The study highlights the translational value of the DBA/2 mouse model for predicting therapeutic efficacy.
• The findings suggest that mood stabilizers with diverse mechanisms of action can normalize PPI deficits.
• This model shows promise for identifying novel therapeutic agents for schizophrenia and bipolar disorder.