Effects of activation and inhibition of cAMP-dependent protein kinase on long-term habituation in the crab Chasmagnathus

Abstract

On sudden presentation of a danger stimulus, the crab Chasmagnathus elicits an escape response that habituates promptly and for a long period. We have previously reported that administration of a CAMP-permeable analog (CPT-CAMP) along with a phosphodiesterase inhibitor (IBMX) improves long-term habituation (LTH). In present experiments we studied the effect of systemic administration of the protein kinase A (PKA) activator Sp-5,6-DCI-cBIMPS and that of the PKA inhibitor Rp-8-Cl-cAMPS on LTH tested 24 h after a weak training protocol (5 trials of danger stimulus presentation) or a strong training protocol (15–30 trials), respectively. A 50 μl pre-training injection of 75 μM Sp-5,6-DCI-cBIMPS, and to a lesser degree of 25 μM improved retention of the habituated response but not affect short-term habituation (STH). Like pre-training injection, post-training administration of Sp-5,6-DCI-cBIMPS proved to exert a facilitatory action on retention though with 75 μM dose only. Conversely, both pre- and post-training injection of 25 μM Rp-8-Cl-cAMPS impaired LTH without affecting STH. Thus, the PKA activator Sp-5,6-DCI-cBIMPS enables a weak training to produce LTH while the PKA inhibitor Rp-8-Cl-cAMPS impairs LTH when a strong training is given. Activation of crab PKA by Sp-5,6-DCI-cBIMPS and its inhibition by Rp-8-Cl-cAMPS were assessed using an in vitro PKA activity assay. These results provide independent evidences supporting the view that PKA plays a key role in long-term memory storage in this learning paradigm.