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?(Fig.2B1)2B1) and obese mice (Fig. ?(Fig.2B2).2B2). FF of putative VTA dopamine neurons was 2.0 �� 0.4 Hz in lean mice (n = 10) and 2.3 �� 0.3 Hz in obese mice (n = 10); there was no significant difference between the two groups. AP current duration of putative VTA dopamine neurons was 1.49 �� 0.04 ms in lean mice (n = 10) and 1.49 �� 0.04 ms in obese mice (n = 10); there was no significant difference between the two groups. Figure 1. Single�\dose application of quinpirole to VTA neurons in lean and obese mice. (A1) Spontaneous firing records before, during, and after application of 100 nmol/L quinpirole in lean mice. Scale bars, 20 pA; 2 sec. (A2) Spontaneous firing records ... Figure 2. Quinpirole�\induced inhibition of putative VTA dopamine neurons in lean and obese mice. Time courses of normalized FF of VTA neurons in [http://www.selleckchem.com/products/byl719.html Alpelisib cell line] lean (open circles) and obese mice (closed circles) [https://en.wikipedia.org/wiki/Dabigatran Dabigatran] before, during, and after single�\dose application ... Firing inhibition by stepwise quinpirole application We next examined the spontaneous firing of VTA neurons using quinpirole by stepwise application increasing quinpirole concentrations of 3, 10, 30, and 100 nmol/L (Fig. ?(Fig.3).3). In lean mice, quinpirole with concentration of 100 nmol/L ceased spontaneous firing (Fig. ?(Fig.3A1).3A1). In contrast, the same concentration of quinpirole did not cease spontaneous firing in obese mice (Fig. ?(Fig.3A2).3A2). Figure 2B shows the time courses of quinpirole�\induced inhibition in VTA neurons from lean and obese mice. In obese mice, desensitization of quinpirole�\induced inhibition was prominent by subsequently applied quinpirole. Quinpirole�\induced inhibition of FF was significantly decreased in obese mice (Fig. ?(Fig.3B2)3B2) compared with lean mice (Fig. ?(Fig.3B1).3B1). (P [http://www.selleckchem.com/products/Bosutinib.html Bosutinib] ANOVA) The VTA neurons examined by the stepwise application protocol met the criteria for putative dopamine neurons in lean (Fig. ?(Fig.3C1)3C1) and obese mice (Fig. ?(Fig.3C2).3C2). FF of putative VTA dopamine neurons was 2.0 �� 0.2 Hz in lean mice (n = 11) and 2.0 �� 0.3 Hz in obese mice (n = 7); there was no significant difference between the two groups. AP current duration of putative VTA dopamine neurons was 1.60 �� 0.07 ms in lean mice (n = 11) and 1.57 �� 0.07 ms in obese mice (n = 7); there was no significant difference between the two groups. Figure 3. Stepwise application of quinpirole to putative VTA dopamine neurons in lean and obese mice. Spontaneous firing of VTA neurons before, during, and, after application of quinpirole (30 and 100 nmol/L) in lean mice (A1) and obese mice (A2). Time courses ... Quinpirole�\induced firing inhibition by single�\dose and stepwise application As shown in Fig. ?Fig.