Mood stabilizers increase prepulse inhibition in DBA/2NCrl mice

Lithium and several antiepileptic drugs have mood-stabilizing effects in bipolar disorder and schizophrenia. Both disorders are characterized by deficits in prepulse inhibition (PPI) of the acoustic startle response. Using the DBA/2 model of naturally low PPI, which is reliably increased by antipsychotics, five mood stabilizers in clinical use were tested to determine whether they would also increase PPI in this model. All drugs were administered intraperitoneally (i.p.) 30 min before testing. Lithium chloride (30 mg/kg), topiramate (100 and 300 mg/kg), carbamazepine (30, 60, and 100 mg/kg), valproic acid (178 and 316 mg/kg), and lamotrigine (3, 10, and 30 mg/kg) increased percent PPI. The antiepileptic drugs carbamazepine, valproic acid, and lamotrigine at high doses also decreased no-stimulus amplitudes and increased startle amplitudes. At high doses of carbamazepine, valproic acid, and lamotrigine, increases in percent PPI were independent of the increases in startle amplitude. The demonstrated efficacy of five mood stabilizers in the DBA/2 model of naturally low PPI points to the translational value of this model in predicting therapeutic activity in schizophrenia and bipolar disorder of compounds with diverse mechanisms of action.