Dopamine D1 receptors regulate protein synthesis-dependent long-term recognition memory via extracellular signal-regulated kinase 1/2 in the prefrontal cortex
Abstract
Several lines of evidence suggest that extracellular signal-regulated kinase1/2 (ERK1/2) and dopaminergic system is involved in learning and memory. However, it remains to be determined if the dopaminergic system and ERK1/2 pathway contribute to cognitive function in the prefrontal cortex (PFC). The amount of phosphorylated ERK1/2 was increased in the PFC immediately after exposure to novel objects in the training session of the novel object recognition test. An inhibitor of ERK kinase impaired long-term recognition memory 24 h after the training although short-term memory tested 1 h after the training was not affected by the treatment. The dopamine D1 receptor agonist increased ERK1/2 phosphorylation in the PFC in vivo as well as in cortical neurons in vitro. Microinjection of the dopamine D1 receptor antagonist into the PFC impaired long-term recognition memory whereas the D2 receptor antagonist had no effect. Immunohistochemistry revealed that exposure to novel objects resulted in an increase in c-Fos expression in the PFC. Microinjection of the protein synthesis inhibitor anisomycin into the PFC impaired the long-term recognition memory. These results suggest that the activation of ERK1/2 following the stimulation of dopamine D1 receptors is necessary for the protein synthesis-dependent long-term retention of recognition memory in the PFC.
Footnotes
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↵3 Correspondence author.
↵3 E-mail kyamada{at}p.kanazawa-u.ac.jp; fax +81-76-234-4416.
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Article is online at http://www.learnmem.org/cgi/doi/10.1101/lm.461407
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- Received November 6, 2006.
- Accepted January 9, 2007.
- Copyright © 2007, Cold Spring Harbor Laboratory Press