Vasopressin-deficient rats exhibit sensorimotor gating deficits that are reversed by subchronic haloperidol

Background: Brattleboro (BB) rats are Long Evans rats with a single base pa ir genetic mutation that impairs their ability, to synthesize vasopressin, a neurotransmitter and neurohormone. Brattleboro rats are known to have def icits in memory, emotional reactivity, motivation, attention, and social re cognition, abnormalities associated with schizophrenia. Prepulse inhibition (PPI) of the acoustic startle reflex (ASR) is a measure of sensorimotor ga ting. Prepulse inhibition is deficient in unmedicated schizophrenia patient s, and PPI deficits in schizophrenia may be related to the cognitive and be havioral abnormalities associated with this disorder. In this study we test ed the hypothesis that BB rats exhibit PPI deficits analogous to those exhi bited by schizophrenia patients. Methods: In one experiment, BB rats homozygous (BB-Ho) or heterozygous (BB- Hz) for the mutated vasopressin gene were compared with normal Long Evans ( LE) rats from the same breeder source. In separate studies, BB-Ho and LE ra ts were treated with acute or subchronic (22 days) injections of haloperido l. Results: Both BB-Ho and BB-Hz rats had significantly, higher ASR and signif icantly lower PPI compared with LE rats, with BB-Ho rats exhibiting the low est PPI among all three genotypes. Furthermore, a single subcutaneous (SC) injection of haloperidol (0.5 mg/kg) did not reverse the PPI deficits in BB rats. In contrast, daily SC administration of haloperidol for 22 days reve rsed PPI deficits in BB rats. Conclusions: These results suggest that PPI deficient BB rats may, be an im portant genetic model of PPI deficits, which may help elucidate genetic, ph armacologic, and pathophysiologic mechanisms underlying PPI deficits and th e effects of antipsychotic drugs on PPI. Biol Psychiatry 2001;50:425-433 (C ) 2001 Society, of Biological Psychiatry.