A rapidly acquired one-way conditioned avoidance procedure in rats as a primary screening test for antipsychotics: influence of shock intensity on avoidance performance.
Antipsychotics selectively disrupt relatively weak responses maintained by conditioned stimuli compared with stronger responses maintained by unconditioned stimuli. The present study describes an easily taught and rapidly acquired (within one 15-trial session) one-way conditioned avoidance procedure for rats suitable for screening of drugs for potential antipsychotic activity. This was achieved by using an easily acquired response (running, part of the species-specific defense reaction repertoire), a clearly discriminated conditioned stimulus and determination of the appropriate strength of the unconditioned stimulus (i.e. shock level) for this procedure. Behavior acquired under these described conditions resulted in stable performance over long retest periods. By using either a low or high intensity of shock level under which the animals were trained and tested, the difference between the dose of haloperidol and chlorpromazine able to disrupt avoidance and that which disrupted escape response rates was increased. This effect was also observed for morphine, which inhibited both avoidance and escape responses at similar dose levels only under low shock conditions. At a high shock condition morphine more selectively inhibited avoidance responding. Diazepam did not affect avoidance behavior under the conditions described here.
van der Heyden
J A
JA
Department of Pharmacology, Duphar B.V., Weesp, The Netherlands.
Bradford
L D
LD
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects*; D002746:Chlorpromazine / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004597:Electroshock; D004924:Escape Reaction / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D009020:Morphine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects
D014150:Antipsychotic Agents; D009020:Morphine; D006220:Haloperidol; D003975:Diazepam; D002746:Chlorpromazine