Protein kinase C inhibitor chelerythrine disrupts memory formation in chicks.

Abstract

Chelerythrine (CHELE), a specific, potent protein kinase C (PKC) inhibitor, disrupts memory formation for a one-trial peck-avoidance task. Three predictions were made about how CHELE, injected into chick brain near the time of training, would affect memory formation, based on previous work with two classes of protein kinase inhibitors (M. R. Rosenzweig et al., 1992; P. A. Serrano et al., 1994) and the in vitro inhibition of PKC by CHELE: (a) CHELE, injected into the intermediate medial hyperstriatum ventrale, would significantly impair memory formation; (b) the amnestic dose would be approximately 10 nmol; (c) CHELE would not produce amnesia for about 45 min after training, but significantly impair memory by 60 min. Experimental tests confirmed each prediction. This study adds to evidence that PKC activity is part of a cascade of neurochemical events initiated by learning and that PKC activity shortly after training is necessary for long-term memory.