Schizophrenic-like sensorimotor gating abnormalities in rats following dopamine infusion into the nucleus accumbens.
Previous studies have demonstrated that several dopamine agonists disrupt sensorimotor gating as measured by prepulse inhibition (PPI) of the acoustic startle response (ASR) in rats. Schizophrenic patients also exhibit deficits in PPI when the prepulse precedes the startle stimulus by less than 500 ms. In experiment 1, dopamine (0-40 micrograms) infused directly into the nucleus accumbens in rats caused a dose-dependent decrease in PPI at prepulse intervals shorter than 500 ms. In experiment 2, this effect of accumbens dopamine infusion on sensorimotor gating was found to vary with changes in prepulse intensity. These findings strongly suggest that increased mesolimbic dopamine activity is one substrate of the sensorimotor gating deficits in rats that are caused by treatment with dopamine agonists; similar substrates might mediate deficits in PPI exhibited by schizophrenic patients.
Swerdlow
N R
NR
Department of Psychiatry, University of California, San Diego, La Jolla 92093.
Braff
D L
DL
Masten
V L
VL
Geyer
M A
MA
D000818:Animals; D004298:Dopamine / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006892:Hydroxydopamines / Q000494:pharmacology; D007267:Injections; D008032:Limbic System / Q000502:physiology; D008297:Male; D009046:Motor Neurons / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D009714:Nucleus Accumbens; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D012559:Schizophrenia / Q000503:physiopathology*; D012686:Septal Nuclei
D006892:Hydroxydopamines; D016627:Oxidopamine; D004298:Dopamine