Stimulators of the cAMP cascade reverse amnesia induced by intra-amygdala but not intrahippocampal KN-62 administration.
Infusion of the calcium-calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-62 (3.5 ng/side) 0 h after training into rat hippocampus CA1 or amygdala has been known for years to cause retrograde amnesia for step-down inhibitory avoidance. On the other hand, drugs that indirectly stimulate protein kinase A (PKA) (8-Br-cAMP, 1.25 microg/side; norepinephrine, 0.3 microg/side; the dopamine D1 receptor agonist, SKF38393, 7.5 microg/side) infused 3 h posttraining into CA1 but not amygdala markedly facilitate retention of this task. Here we find that 8-Br-cAMP, norepinephrine, or SKF38393 given 3 h posttraining into rat CA1 reverses the amnestic effect of KN-62 given into the amygdala 0 h after training, but not that of KN-62 given into CA1 0 h posttraining. The findings bear on the participation of CaMKII and of the cAMP/PKA cascade in memory processes in the hippocampus and the amygdala. Both cascades have been proposed to play a role in memory: CaMKII in the early phase and PKA in the transition between the early phase and long-term memory. Clearly, in CA1, both cascades are involved and are crucial, and the CaMKII cascade must precede the PKA cascade. In contrast, in the amygdala, only the CaMKII cascade is active, and it does not play a central role in memory, inasmuch as its deleterious effect may be fully recovered by stimulation of the PKA cascade in the hippocampus. This further supports the contention that the hippocampus is essential for memory formation of this task, as it is for many others, whereas the amygdala appears to play instead an early modulatory role.
Barros
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DM
Centro de Memoria, Departamento de Bioquímica, Instituto de Ciencias Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcellos 2600, Porto Alegre, RS, 90035-003, Brazil.
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Sant'Anna
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Quevedo
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Medina
J H
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McGaugh
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JL
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D007267:Injections; D008297:Male; D011939:Mental Recall / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012153:Retention, Psychology / Q000187:drug effects*
D004791:Enzyme Inhibitors; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases