2, left panels) The filled symbols in left panels of Figure 2 show the percentage of responses made on the cocaine-associated lever (Fig. rats to discriminate the effects of nicotine or cocaine. = 12; 330 ? 370g) were obtained from Charles River (Wilmington, MA) and housed in a temperature- and humidity-controlled room. Animals used in this study were maintained in facilities fully accredited by the American Association for the Accreditation of Laboratory Animal Care (AAALAC) and all experiments were conducted in accordance with the guidelines of the Institutional Care and Use Committee of the Intramural Research Program, National Institute on Drug Abuse (NIDA), National Institutes of Health and the Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research (National Research Council, 2003). Experiments were conducted during the light phase of a 12-h/12-h light/dark cycle (lights on at 0700 hours). Rats were housed individually and water was available = 0.18). One-way ANOVA also indicated an absence of effect of topiramate treatment alone on rates of responding (= 0.8). b) Effect of topiramate on discrimination of the training dose of nicotine (Fig.1, left panels) The filled symbols in the left panels of Figure 1 show the percentage of responses made on the nicotine-associated lever (Fig. 1A) and overall rates of responding (Fig. 1C) during sessions when different doses of topiramate were tested for their ability to alter the discriminative-stimulus effects of the 0.4 mg/kg training dose of nicotine. Analysis of the discrimination performance of the rats indicates that topiramate did not alter the discriminative-stimulus effects of the 0.4 mg/kg training dose of nicotine, even at the highest (i.e. 60 mg/kg) topiramate dose tested (= 0.5; Fig. 1A). Topiramate given in combination with nicotine slightly depressed rates of responding at high doses, but this effect was not significant (= 0.25; Fig. 1C). Effects of topiramate on discrimination of various doses of nicotine (right panels Fig. 1) The right panels of Figure 1 show the effects of 10, 30 and 60 mg/kg topiramate on the dose-response curve for nicotine discrimination (Fig. 1B) and on overall rates of responding (Fig. 1D). A two-way ANOVA analysis of results of discrimination performance indicated a significant effect of nicotine dose ( 0.0001), no significant effect of topiramate pretreatment (= 0.45), and no significant interaction between topiramate pretreatment and nicotine dose (= 0.8). A two-way ANOVA analysis of results of rates of responding indicated no significant effect of nicotine dose (= 0.8), no significant effect of topiramate pretreatment (= 0.32), and no significant interaction between topiramate pretreatment and nicotine dose (= 0.7). ED50 values for drug-lever selection with 95% CIs are shown in Table 1. The ED50 values overlap confirming that topiramate produced no significant shift of the dose-response curves for nicotine discrimination. Table 1 ED50 values (95% CIs) for percentage of drug-lever selection when nicotine or cocaine were administered alone and with various doses of topiramate = 0.23). One-way ANOVA also indicated an absence of effect of topiramate treatment alone on rates of responding (= 0.8). b) Effect of topiramate on discrimination of the training dose of cocaine (Fig. 2, left panels) The filled symbols in left panels of Figure 2 show the percentage of responses made on the cocaine-associated lever (Fig. 2A) and overall rates of responding (Fig. 2C) during sessions when different doses of topiramate were tested for their ability to alter the discriminative-stimulus effects of the 10 mg/kg training dose of cocaine. Analysis of the discrimination performance of the rats indicates that topiramate did not alter the discriminative-stimulus effects of the 10 mg/kg training dose of cocaine, even at the highest topiramate dose tested (= 0.4; Fig. 2A). Topiramate given in AGN 194310 combination with 10 mg/kg cocaine did not affect rates of responding compared to cocaine alone, even at high doses (= 0.6; Fig. 2C). Effects of topiramate on discrimination of various doses of cocaine (right panels Fig. 2) The right panels of Figure 2 show the effects of 10 and 30 mg/kg topiramate on the dose-response curve for cocaine discrimination (Fig. 2B) and on overall rates of responding (Fig. 2D). A two-way ANOVA analysis of results of discrimination performance indicated a significant effect of cocaine dose ( .Topiramate given in combination with nicotine slightly depressed rates of responding at high doses, but this effect was not significant (= 0.25; Fig. the guidelines of the Institutional Care and Use Committee of the Intramural Research Program, National Institute on Drug Abuse (NIDA), National Institutes of Health and the Guidelines for the Care and Use of Mammals in Neuroscience and AGN 194310 Behavioral Research (National Research Council, 2003). Experiments were conducted during the light phase of a 12-h/12-h light/dark cycle (lights on at 0700 hours). Rats were housed individually and water was available = 0.18). One-way ANOVA also indicated an absence of effect of topiramate treatment alone on rates of responding (= 0.8). b) Effect of topiramate on discrimination of the training dose of nicotine (Fig.1, left panels) The filled symbols in the left panels of Figure 1 show the percentage of responses made on the nicotine-associated lever (Fig. 1A) and overall rates of responding (Fig. 1C) during sessions when different doses of topiramate were tested for their ability to alter the discriminative-stimulus effects of the 0.4 mg/kg training dose of nicotine. Analysis of the discrimination performance of the rats indicates that topiramate did not alter the discriminative-stimulus effects Rabbit polyclonal to Ly-6G of the 0.4 mg/kg training dose of nicotine, even at the highest (i.e. 60 mg/kg) topiramate dose tested (= 0.5; Fig. 1A). Topiramate given in combination with nicotine slightly depressed rates of responding at high doses, but this effect AGN 194310 was not significant (= 0.25; Fig. 1C). Effects of topiramate on discrimination of various doses of nicotine (right panels Fig. 1) The right panels of Figure 1 show the effects of 10, 30 and 60 mg/kg topiramate on the dose-response curve for nicotine discrimination AGN 194310 (Fig. 1B) and on overall rates of responding (Fig. 1D). A two-way ANOVA analysis of results of discrimination performance indicated a significant effect of nicotine dose ( 0.0001), no significant effect of topiramate pretreatment (= 0.45), and no significant interaction between topiramate pretreatment and nicotine dose (= 0.8). A two-way ANOVA analysis of results of rates of responding indicated no significant effect of nicotine dose (= 0.8), no significant effect of topiramate pretreatment (= 0.32), and no significant interaction between topiramate pretreatment and nicotine dose (= 0.7). ED50 values for drug-lever selection with 95% CIs are shown in Table 1. The ED50 values overlap confirming that topiramate produced no significant shift of the dose-response curves for nicotine discrimination. Table 1 ED50 values (95% CIs) for percentage of drug-lever selection when nicotine or cocaine were administered alone and with various doses of topiramate = 0.23). One-way ANOVA also indicated an absence of effect of topiramate treatment alone on rates of responding (= 0.8). b) Effect of topiramate on discrimination of the training dose of cocaine (Fig. 2, left panels) The filled symbols in left panels of Figure 2 show the percentage of responses made on the cocaine-associated lever (Fig. 2A) and overall rates of responding (Fig. 2C) during sessions when different doses of topiramate were tested for their ability to alter the discriminative-stimulus effects of the 10 mg/kg training dose of cocaine. Analysis of the discrimination performance of the rats indicates that topiramate did not alter the discriminative-stimulus effects of the 10 mg/kg training dose of cocaine, even at the highest topiramate dose tested (= 0.4; Fig. 2A). Topiramate given in combination with 10 mg/kg cocaine did not affect rates of responding compared to cocaine alone, even at high doses (= 0.6; Fig. 2C). Effects of topiramate on discrimination of various doses of cocaine (right panels Fig. 2) The right panels of Figure 2 show the effects of 10 and 30 mg/kg topiramate on the dose-response curve for cocaine discrimination (Fig..