Effects of activation and inhibition of cAMP-dependent protein kinase on long-term habituation in the crab Chasmagnathus.
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-DCl-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 microliters pre-training injection of 75 microM Sp-5,6-DCl-cBIMPS, and to a lesser degree of 25 microM, improved retention of the habituated response but not affect short-term habituation (STH). Like pre-training injection, post-training administration of Sp-5,6-DCl-cBIMPS proved to exert a facilitatory action on retention though with 75 microM dose only. Conversely, both pre- and post-training injection of 25 microM Rp-8-Cl-cAMPS impaired LTH without affecting STH. Thus, the PKA activator Sp-5,6-DCl-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-DCl-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.
Facultad de Ciencias Exactas y Naturales, Departamento de Ciencias Biológicas, Pab 2. University of Buenos Aires, Argentina. aromano@biolo.bg.uba.edu.ar
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Romano
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Locatelli
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Delorenzi
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Pedreira
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Maldonado
D000647:Amnesia / Q000139:chemically induced; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D003386:Brachyura; D001923:Brain Chemistry; D003213:Conditioning, Psychological / Q000187:drug effects; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004004:Dichlororibofuranosylbenzimidazole / Q000031:analogs & derivatives / Q000494:pharmacology; D017952:Ganglia, Invertebrate / Q000737:chemistry; D006185:Habituation, Psychophysiologic / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects; D013873:Thionucleotides / Q000494:pharmacology
D000970:Antineoplastic Agents; D013873:Thionucleotides; C071644:5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole-3',5'-monophosphorothioate; C074155:8-chloroadenosine-3',5'-cyclic monophosphorothioate; D004004:Dichlororibofuranosylbenzimidazole; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases