Ameliorating schizophrenia-like symptoms in vasopressin deficient male Brattleboro rat by chronic antipsychotic treatment

Abstract

Due to its various function vasopressin has been associated with many psychiatric disorders, including schizophrenia. Our previous study confirmed that vasopressin-deficient (di/di) Brattleboro rat can be a good genetic model for schizophrenia. Our present aim was to confirm whether the treatment effects of marketed antipsychotics are similar in di/di rats to those seen in human schizophrenic patients.Chronic subcutaneous administration of aripiprazole (5 mg/kg), clozapine (1 mg/kg), haloperidol (0.1 mg/kg), olanzapine (0.3 mg/kg) or risperidone (0.25 mg/kg) was used for 15 days in control (+/+ Brattleboro) and di/di rats. Social discrimination, social avoidance and prepulse inhibition tests were conducted on day 1, 8 and 15 of the treatment.Vasopressin-deficient rats showed social memory- and sensorimotor gating deficit. All used antipsychotics successfully normalized the reduced prepulse inhibition of di/di animals. However, most were effective only after prolonged treatment. Aripiprazole, clozapine, and olanzapine normalized the social memory deficit, while the effects of haloperidol and risperidone were not unequivocal. All drugs reduced social interest to some extent both in control and in di/di animals, aripiprazole being the less implicated in this regard during the social avoidance test.The restoration of schizophrenia-like behavior by antipsychotic treatment further support the utility of the vasopressin-deficient Brattleboro rat as a good preclinical model. Reduced social interest might be a general side-effect of antipsychotics, and aripiprazole has the most favorable profile in this regard.