Background:

SL-327 is a selective inhibitor of MEK1 and MEK2 with IC50 values of 0.18 and 0.22μM,  respectively.
MEK1 and MEK2 (ERK) are a kinase enzyme which phosphorylate mitogen-activated protein kinase (MAPK). Extracellular signal-regulated kinase (ERK) activity is essential for the acquisition of associative learning tasks.
In adult male CD-1 mice, SL-327 inhibited Pp-ERK immunostaining in the nuclei of the cells induced by cocaine. SL-327 pretreatment inhibited c-Fos expression in nuclear and inhibited activation of ERK within all the amygdala, namely LA, BLA, BMP, Ce and MePD [1]. In morphine-pretreated rats, SL-327 increased (58%) the expression of morphine-induced psychomotor sensitization (SW3) and fully prevented the upregulation of p-PEA-15, p-FADD, and p-Akt1 at SW3 [2]. In adult male DBA/2J mice, SL-327 significantly reduced pERK levels by 40% in both the motor cortex and dorsal striatum [3]. In rat model, SL-327 inhibited MAPK/ERK cascade, which prevented LTP-dependent gene induction and CREB and Elk-1 phosphorylation, resulting in rapidly decaying LTP [4].
参考文献:
[1]. Radwanska K, Caboche J, Kaczmarek L. Extracellular signal-regulated kinases (ERKs) modulate cocaine-induced gene expression in the mouse amygdala. Eur J Neurosci, 2005, 22(4): 939-948.
[2]. Ramos-Miguel A, Esteban S, García-Sevilla JA. The time course of unconditioned morphine-induced psychomotor sensitization mirrors the phosphorylation of FADD and MEK/ERK in rat striatum: role of PEA-15 as a FADD-ERK binding partner in striatal plasticity. Eur Neuropsychopharmacol, 2010, 20(1): 49-64.
[3]. Groblewski PA, Franken FH, Cunningham CL. Inhibition of extracellular signal-regulated kinase (ERK) activity with SL327 does not prevent acquisition, expression, and extinction of ethanol-seeking behavior in mice. Behav Brain Res, 2011, 217(2): 399-407.
[4]. Davis S, Vanhoutte P, Pages C, et al. The MAPK/ERK cascade targets both Elk-1 and cAMP response element-binding protein to control long-term potentiation-dependent gene expression in the dentate gyrus in vivo. J Neurosci, 2000, 20(12): 4563-4572.