+ and 4 CS?trials followed by a preference test, the results of which are shown in Figure 1. ANOVA showed that dose of cocaine at conditioning had a significant impact on CS+ time [F(2,56) = 8.8, p 0.0005; Figure 1A). Post-hoc tests demonstrated that each 20 and 5 mg/kg doses generated extra preference than did 2 mg/kg, and that preference in 20 mg/kg treated mice was higher than that of five mg/kg. Moreover, to demonstrate linearity of these effects, data are plotted as log doses alongside a linear function (Figure 1A). Examination of preference (G+ vs G-) within each therapy situation showed that whilst 20 mg/kg [t(21) = 6.two, p 0.00005] and five mg/kg [t(19) = 2.5, p 0.05] cocaine developed preference, two mg/kg didn’t (Figure 1B). Experiment 2: NaBut Enhances Initial Conditioning of Cocaine-Induced CPP To examine effects of NaBut on CPP conditioning, mice were conditioned using a lower dose of cocaine (5 mg/kg) with fewer pairings (3 CS+ trials followed by injections of NaBut (0, 0.3, 0.six, or 1.2 g/kg) and three CS?trials followed by automobile injection). This reduction in trial quantity using a low dose of CPP ought to lead to only a moderate preference creating in vehicle-treated animals, which makes it possible for NaBut-induced enhancements to be detected. ANOVA showed an impact of NaBut therapy on CS+ time [F(3,57) = four.2, p 0.01; Figure 2A]. Post-hoc tests showed that 1.two g/kg NaBut enhanced preference in comparison with all other treatment groups, suggesting that a high-dose of NaBut enhanced acquisition of weak CPP (Figure 2A).3-Bromo-5-fluoro-4-methylbenzoic acid Order Examination of preference (G+ vs G-) inside therapy situations showed that mice treated with 0.2-Cyclopentenone site three or 1.PMID:23614016 two g/kg NaBut showed considerable CPP [0.3 g/kg, t(15) = three.0, p 0.01; 1.2 g/kg, t(15) = six.0, p 0.00005; Figure 2B]. Experiment 3: NaBut Modulates Extinction of Cocaine-Induced CPP To investigate the effects of NaBut on extinction, mice were 1st conditioned with two CS+ 20 mg/kg cocaine, and CS?saline trials. Twenty-four hours later preference was assessed (Preference in Table 1). Mice had been then assigned to NaBut remedy groups, and received 4 extinction sessions (EXT1?) followed by NaBut (0, 0.3, 0.6, 1.two g/kg) administration (Figure three). Mice then received an extra preference test (EXT5) followed by reconditioning. 1 (Reconditioning) and 21 days (Retention) soon after reconditioning mice had been once more assessed for preference (Figure 4). Extinction–Figure three shows that preference in every dose decreased more than the course of extinction. Repeated-measures ANOVA showed that across extinction there was a key impact of session [F(1,46) = 33.9, p = 0.0000005], but no drug effects and no interaction. Closer examination of preference (G+ vs G-) within each dose through extinction (Table 1) showed that all groups stopped expressing a preference by the final extinction session, but that this occurred sooner in subjects treated with 0.three or 0.6 g/kg NaBut.Pharmacol Biochem Behav. Author manuscript; out there in PMC 2014 May well 01.Raybuck et al.PageReconditioning and Retention–Figure 4 shows that reconditioning was impaired in animals that received 0.3 mg/kg NaBut during extinction. An ANOVA on CS+ time following reconditioning (Figure 4A) showed an impact of NaBut [F(three,44) = 3.eight, p = 0.0165], and post-hoc tests showed that mice treated with 0.3 g/kg NaBut soon after extinction showed significantly less reconditioned preference in comparison to vehicle-treated controls, suggesting that this low-dose enhanced extinction resulting in higher resistance to re.
