Kana Isotani

Wakayama Medical University, Wakayama, Wakayama, Japan

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Publications (3)14.14 Total impact

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    ABSTRACT: 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 04/2011; 65(10):1052-61. · 2.31 Impact Factor
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    ABSTRACT: The present study was undertaken to identify possible similarities between the effects of kappa-opioid receptor agonist, N-methyl-D-aspartate-receptor antagonist, and sigma receptor agonist on the discriminative stimulus effects of U-50488H, and the possible involvement of sigma receptors in the discriminative stimulus and aversive effects of U-50488H. The kappa-opioid receptor agonist U-50488H produced significant place aversion as measured by the conditioned place preference procedure, and this effect was completely abolished by treatment with the putative sigma-1 receptor antagonist NE-100. In addition, phencyclidine (+)-SKF-10047 and (+)-pentazocine, which are sigma receptor agonists, generalized to the discriminative stimulus effects of U-50488H in rats that had been trained to discriminate between U-50488H (3.0 mg/kg) and saline. Furthermore, NE-100 significantly attenuated the discriminative stimulus effects of U-50488H and the U-50488H-like discriminative stimulus effects of phencyclidine. These results suggest that the sigma-1 receptor is responsible for both the discriminative stimulus effects and aversive effects of U-50488H.
    Addiction Biology 03/2011; 17(4):717-24. · 5.91 Impact Factor
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    ABSTRACT: Substitutions of the dopamine D(2) or D(3) receptor agonists for the discriminative stimulus effect induced by U-50,488H, methamphetamine (METH) and cocaine in rats were examined. The D(2) receptor agonist R-propylnorapomorphine [(-)-NPA] failed to substitute for U-50,488H cue, while the D(3) receptor-preferred agonist (+/-)-7-hydroxy-dipropylaminotetralin hydrobromide (7-OH-DPAT) produced dose-related increases in drug-appropriate responding up to 0.03 mg/kg, which fully substituted. At doses greater than 0.03 mg/kg of 7-OH-DPAT, there was a dose-dependent decrease in the percentage of responses on the U-50,488H-appropriate lever. Furthermore (-)-NPA and 7-OH-DPAT at high doses substituted for the discriminative stimulus effect induced by both METH and cocaine, indicating that 7-OH-DPAT at high doses may interact with D(2) receptors. These results suggest that the stimulation of D(2) receptor may be critical for the production of the discriminative stimulus effect induced by METH and cocaine, whereas the stimulation of D(3) receptor may contribute to the production of the U-50,488H cue.
    Addiction Biology 11/2010; 17(6):949-55. · 5.91 Impact Factor