Analysis of long-term cognitive-enhancing effects of bryostatin-1 on the rabbit (Oryctolagus cuniculus) nictitating membrane response.

Previous work demonstrated that protein kinase C (PKC) is implicated in learning and memory. This study investigated whether: (i) PKC activated by bryostatin-1 (Bryo) just before or just after sessions of classical conditioning was capable of enhancing classical conditioning of the rabbit nictitating membrane response; (ii) improved behavioral performance matched the time course of PKC activation induced by Bryo; and (iii) vitamin E (Vit E) enhanced the efficacy of Bryo. Paired rabbits received daily trace conditioning with a tone conditioned stimulus and a corneal air puff unconditioned stimulus. Unpaired rabbits received the same stimuli but in an explicitly unpaired manner. After trace conditioning, all rabbits received daily delay conditioning, and then tone intensity testing. Rabbits pretreated with 10 microg/kg Bryo every other day before a relatively simple trace conditioning task showed more conditioned responses (CRs) during the first 10 trials of each trace conditioning session and a higher likelihood of a CR on the first trial of each trace conditioning session than rabbits pretreated with the vehicle control. Rabbits either posttreated daily with 10 microg/kg Bryo or pretreated with Vit E and subjected to a difficult trace conditioning task showed increased CRs relative to the vehicle control. Neither Bryo nor Vit E or their combination altered nonassociative responding or altered sensitivity to the conditioned stimulus or unconditioned stimulus. These findings demonstrate Bryo has long-term enhancing effects on classical conditioning of the rabbit nictitating membrane response.