Sensory gating in rats depleted of dopamine as neonates: potential relevance to findings in schizophrenic patients.
Based on a recent hypothesis of reduced subcortical dopaminergic tone, evidence of early neurodevelopmental deviation, and acoustic startle abnormalities in schizophrenia, we examined acoustic startle in adult animals depleted of dopamine (DA) as neonates. Male rat pups received intracerebroventricular injections of either 6-hydroxydopamine (6-OHDA, 100 micrograms) or its vehicle on postnatal day 3. At 60 days of age, baseline startle and prepulse inhibition (PPI) of startle were assessed in a no injection condition, with all other animals receiving injections of saline or the DA agonist, apomorphine. Acoustic startle was elicited using 120 db white noise bursts alone or preceded by prepulses of 75, 80, and 85 db. Animals treated with 6-OHDA exhibited a 93% depletion of striatal DA compared to vehicle-treated controls. Whereas DA depleted animals did not differ from controls in the no injection condition, they showed greater baseline startle and reduced PPI compared to controls after saline injections. Depleted animals also showed exaggerated responses to apomorphine, with greater increases in baseline startle, loss of habituation, and decreased PPI compared to controls. Findings indicate that neonatal DA depletions lead to increased baseline startle and impaired sensory gating in adulthood after saline injections and dopamine agonists compared to controls. These findings may be relevant to a subgroup of psychotic patients that exhibit similar startle abnormalities as well as signs of hypodopaminergic function.
Schwarzkopf
S B
SB
Department of Psychiatry, Ohio State University, Columbus 43210.
Mitra
T
T
Bruno
J P
JP
D000161:Acoustic Stimulation; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D001921:Brain / Q000502:physiology*; D002853:Chromatography, Liquid; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects; D004298:Dopamine / Q000032:analysis / Q000502:physiology*; D006185:Habituation, Psychophysiologic; D006801:Humans; D007231:Infant, Newborn; D007276:Injections, Intraventricular; D008297:Male; D008954:Models, Biological; D009434:Neural Pathways / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013216:Reflex, Startle / Q000502:physiology*; D012559:Schizophrenia / Q000209:etiology / Q000503:physiopathology*
D016627:Oxidopamine; D004298:Dopamine