Prepulse inhibition of acoustic startle, a measure of sensorimotor gating: effects of antipsychotics and other agents in rats.
Schizophrenic patients are deficient in various neurologic measures reflecting information processing. One such measure in prepulse inhibition (PPI) of acoustic startle, in which schizophrenics display less inhibition than normal subjects. PPI is also diminished in rats treated with psychotomimetic drugs such as amphetamine and phencyclidine. PPI has been suggested as a model relevant for studying the pathophysiology of schizophrenia. We studied the effect of a variety of antipsychotics and putative antipsychotics and some key reference compounds on the acoustic startle response (ASR) and PPI. Some, but not all, antipsychotics tested (mainly selective dopamine D2 antagonists) enhanced PPI. Remoxipride and clozapine, both of which are antipsychotics, and the very potent and highly selective D2 antagonist, NCQ-298, did not. It is concluded that enhanced PPI in otherwise untreated rats does not reflect antipsychotic efficacy. We further noted that the effect on PPI was independent of the effect on ASR.
Johansson
C
C
Department of Behavioural and Biochemical Pharmacology, Preclinical Research and Development, Astra Arcus AB, Södertälje, Sweden. johansson@arcus.se.astra.com
Jackson
D M
DM
Zhang
J
J
Svensson
L
L
D000161:Acoustic Stimulation; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D008297:Male; D008606:Mental Processes / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects*
D014150:Antipsychotic Agents; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin