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Activation of extracellular signal‐regulated kinase is critical for the discriminative stimulus effects induced by U‐50,488H
Author(s) -
Yoshizawa Kazumi,
Narita Minoru,
Saeki Mai,
Narita Michiko,
Isotani Kana,
Horiuchi Hiroshi,
Imai Satoshi,
Kuzumaki Naoko,
Suzuki Tsutomu
Publication year - 2011
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20937
Subject(s) - nucleus accumbens , signal transduction , mapk/erk pathway , chemistry , kinase , phosphorylation , agonist , receptor , creb , protein kinase a , neuroscience , stimulus (psychology) , extracellular , microbiology and biotechnology , pharmacology , medicine , endocrinology , biology , psychology , biochemistry , transcription factor , psychotherapist , gene
We previously demonstrated that the discriminative stimulus effects of the κ‐opioid receptor agonist U‐50,488H were associated with its aversive effects in rats. However, its molecular signaling mechanisms are not fully understood. The aim of this study was to investigate the intracellular signaling that plays a role in mediating the discriminative stimulus effect induced by U‐50,488H. To better understand the involvement of molecular signaling mechanisms in the discriminative stimulus effects of U‐50,488H, rats were subjected to a drug discrimination paradigm, and levels of immunoreactivity and mRNA expression were determined in these rats. Although U‐50,488H‐trained rats did not show changes in the mRNA expression of typical dopamine (DA) receptors, NMDA receptor subunits, or transcriptional activators, there were remarkable changes in the levels of immunoreactivity of several phosphorylated protein kinases. The levels of immunoreactivity of phosphorylated p38 MAPK and phosphorylated calcium/calmodulin‐dependent protein kinase II (CaMKII) were significantly increased in the nucleus accumbens and amygdala in lever‐press, yoked and discrimination groups compared to a naive group. Furthermore, the level of phosphorylated cAMP response element‐binding protein was also increased in both the discrimination and yoked groups. In contrast, the immunoreactivity of phosphorylated extracellular signaling‐regulated kinase (ERK 1/2) was specifically increased in the discrimination group. These results suggest that the ERK signaling pathway in the nucleus accumbens and amygdala may be critical for the expression of the discriminative stimulus effects of U‐50,488H. Synapse, 2011. © 2011 Wiley‐Liss, Inc.