Effects of sustained cocaine exposure on sensorimotor gating of startle in rats.
Deficient sensorimotor gating, as measured by a relative loss of prepulse inhibition (PPI) of the startle reflex, has been reported in schizophrenia patients and in rats treated acutely with dopamine (DA) agonists or other psychotomimetic agents. For this reason, PPI has been used as a cross-species measure for studying the neurochemistry of specific information processing deficits in schizophrenia. Cocaine is a DA reuptake inhibitor which can precipitate psychosis after sustained use in humans. In rats, sustained exposure to cocaine results in neuropathological and neurochemical changes in several brain regions, and is also associated with specific prolonged behavioral abnormalities. In the present study, we examined the effects of both acute and sustained cocaine administration on PPI and other measures of the startle reflex in rats. Cocaine produced a significant, dose-dependent reduction in PPI, both after acute administration, and after 3 days of sustained administration via implanted subcutaneous pellets. PPI returned to control levels when rats were tested 10 days after sustained (5 day) cocaine administration. The effects of acute cocaine administration on PPI are consistent with those of other DA agonists and psychotomimetics, but PPI does not appear to be sensitive to lasting effects of a method of prolonged cocaine administration associated with neuropathological and neurochemical changes in several brain regions.
Martinez
Z A
ZA
Department of Psychology, University of California, Los Angeles 90028, USA.
Ellison
G D
GD
Geyer
M A
MA
Swerdlow
N R
NR
D000161:Acoustic Stimulation; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D006185:Habituation, Psychophysiologic / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D019370:Observation; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*; D012559:Schizophrenia / Q000503:physiopathology
D018765:Dopamine Uptake Inhibitors; D003042:Cocaine