EFFECTS OF HALOPERIDOL AND SCH-23390 ON ACOUSTIC STARTLE IN ANIMALS DEPLETED OF DOPAMINE AS NEONATES - IMPLICATIONS FOR NEUROPSYCHIATRIC SYNDROMES

Animals depleted of dopamine (DA) in the neonatal period and tested in adulthood exhibit some similarities to patients with schizophrenia, i ncluding increased sensitivity to DA agonists, altered sensitivity to DA receptor antagonists, and abnormalities of the acoustic startle res ponse (ASR). In this study, we examined the contributions of D-1-like and D-2-like DA receptors to ASR measures in animals depleted of DA as neonates, Male rat pups received intracerebroventricular injections o f 6-hydroxydopamine (DA depleted) or its vehicle (controls) at 3 days of age. Animals underwent startle testing as adults (60-75 days of age ) after administration of DA antagonists (haloperidol: 0.1 or 0.3 mg/k g, SCH 23390: 0.01 or 0.05 mg/kg) with and without DA agonist administ ration (apomorphine 0.5 mg/kg). ASR amplitude and prepulse inhibition (PPI: percentage decrease in startle amplitude due to a low intensity prepulse) were measured. DA depleted animals showed increased ASR ampl itude and reduced PPI compared to controls, Administration of D-1-like or D-2-like DA antagonists significantly reduced overall ASR and incr eased PPI in both control and DA depleted animals, with DA depleted an imals showing a relatively greater sensitivity to the D-1-like antagon ist SCH 23390. Findings are discussed in terms of the role of residual DA in mediating ASR phenomena in depleted animals, differences betwee n D-1/D-2 DA receptor mediation of ASR compared to other behaviors in DA depleted animals, and potential implications for neuropsychiatric s yndromes such as schizophrenia.