The modulation of sensorimotor gating deficits by mesolimbic cholecystokinin.
The effects of cholecystokinin (CCK) in an animal model of sensorimotor-gating deficits with strong face, construct and predictive validity for schizophrenia were investigated. Prepulse inhibition (PPI) occurs when a weak acoustic lead stimulus inhibits the startle response to a loud startling stimulus. Infusions of sulfated CCK-8 in the posterior nucleus accumbens potentiated apomorphine-induced disruption of PPI but had no effect on baseline PPI or the amplitude of acoustic startle reflex itself. The results provide evidence that mesolimbic CCK may play a role in regulating sensorimotor gating deficits but contradict earlier notions that CCK agonists may have antipsychotic properties and upon which clinical trials of CCK agonists in schizophrenia were based. Rather, these results suggest that antagonists of CCK may display neuroleptic-like actions on deficits in PPI and may hold greater promise as antipsychotics.
Feifel
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Department of Psychiatry, University of California, San Diego, La Jolla 92093-8620, USA. dfeifel@ucsd.edu
Swerdlow
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NR
D000161:Acoustic Stimulation; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002766:Cholecystokinin / Q000819:agonists / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D007267:Injections; D008032:Limbic System / Q000033:anatomy & histology / Q000502:physiology*; D008297:Male; D009714:Nucleus Accumbens / Q000033:anatomy & histology; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000502:physiology*
D018491:Dopamine Agonists; D002766:Cholecystokinin; D001058:Apomorphine