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 pair genetic mutation that impairs their ability to synthesize vasopressin, a neurotransmitter and neurohormone. Brattleboro rats are known to have deficits in memory, emotional reactivity, motivation, attention, and social recognition, abnormalities associated with schizophrenia. Prepulse inhibition (PPI) of the acoustic startle reflex (ASR) is a measure of sensorimotor gating. Prepulse inhibition is deficient in unmedicated schizophrenia patients, and PPI deficits in schizophrenia may be related to the cognitive and behavioral abnormalities associated with this disorder. In this study we tested the hypothesis that BB rats exhibit PPI deficits analogous to those exhibited 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 rats were treated with acute or subchronic (22 days) injections of haloperidol.


RESULTS
Both BB-Ho and BB-Hz rats had significantly higher ASR and significantly lower PPI compared with LE rats, with BB-Ho rats exhibiting the lowest 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 reversed PPI deficits in BB rats.


CONCLUSIONS
These results suggest that PPI deficient BB rats may be an important genetic model of PPI deficits, which may help elucidate genetic, pharmacologic, and pathophysiologic mechanisms underlying PPI deficits and the effects of antipsychotic drugs on PPI.
Feifel
D
D
Department of Psychiatry, University of California San Diego, 200 West Arbor Drive, San Diego, CA 92103, USA.
Priebe
K
K
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000175:diagnosis; D004334:Drug Administration Schedule; D020233:Gait Disorders, Neurologic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D006220:Haloperidol / Q000008:administration & dosage / Q000627:therapeutic use*; D006579:Heterozygote; D006720:Homozygote; D007266:Inhibition, Psychological; D008297:Male; D051381:Rats; D011910:Rats, Brattleboro; D020318:Rats, Long-Evans; D013216:Reflex, Startle / Q000502:physiology; D014667:Vasopressins / Q000172:deficiency* / Q000235:genetics
D014150:Antipsychotic Agents; D014667:Vasopressins; D006220:Haloperidol