A tripeptide protease inhibitor attenuates conditioned avoidance behavior.
In a single 10-s training trial, hatchling chicks were conditioned to suppress their spontaneous peck response to a small spherical target by coating it with an aversive liquid. A 24-h test trial employing a dry target demonstrated a robust memory for the training manifested in passive avoidance behavior. Leupeptin, a low-molecular-weight antiprotease, injected i.c.v. 1 h or 15 min prior to training attenuated the long-term avoidance response but not the initial training-induced peck suppression. Leupeptin had no effect on memory if given posttraining. A dose response experiment revealed that a 100- or 200-micrograms dose of leupeptin reliably impaired conditioned avoidance, whereas a 25 or 50-micrograms dose was ineffective. A dipeptide leupeptin analog (L-leucyl-L-arginine) possessed one-half the potency of the tripeptide in the memory task, and a different protease inhibitor (aprotinin) failed to effect the conditioned avoidance behavior. The mechanisms by which leupeptin may exert its influence in this behavioral paradigm and others are discussed.
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D003214:Conditioning, Classical / Q000187:drug effects*; D003864:Depression, Chemical; D007276:Injections, Intraventricular; D007976:Leupeptins / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D013997:Time Factors
D007976:Leupeptins; D009842:Oligopeptides; D011480:Protease Inhibitors; C032854:leupeptin