This confirms that the observed effect was pharmacologically specific but relatively short-lasting

This confirms that the observed effect was pharmacologically specific but relatively short-lasting. and increased chow consumption, comparable to effects of sibutramine; however, memantines effects persisted after treatment discontinuation. The effects of the mGluR5 antagonist MTEP (7.5?mg/kg, IP) on food consumption were in the same direction as seen with memantine, but the TH588 hydrochloride observed differences were not significant. In an additional control experiment, sibutramine and memantine reduced unlimited (24?h) TH588 hydrochloride chow intake during the treatment phase. Present results provide evidence that glutamatergic neurotransmission might be involved in the regulation of excessive consumption of highly palatable foods, and suggest that NMDA receptor may be an attractive target for developing obesity and disordered eating pharmacotherapies. test could not be used to test for food and drug-related differences in Experiments 1C3 due to the lack of independence across measurements (i.e., consumption of one food being correlated with consumption of another food) and our interest in consumption changes over time. To address this issue, we used generalized estimating equations (GEE) statistical approach involving estimation of marginal models to fit consumption as a function of drug, food type, phase, and time as well as all their interactions. A backward elimination procedure starting with the four-way interaction was used to select the best-fit, final model. The GEE approach for repeated measurements was used to estimate and test the model. This procedure is best suited to analyze correlated data obtained in longitudinal studies, which allows to test the effect of intervention at various time-points during treatment and at follow-up (Lee et al. 2007; Zeger and Liang 1986). The GEE methodology requires no parametric distribution assumption, provides robust inference with respect to misspecification of the within subject correlation and allows for the analysis of continuous, categorical and count data. TH588 hydrochloride PROC GENMOD in SAS 9.1 was used to carry out analyses. A one-way ANOVA with Tukeys HSD post hoc test was used to conduct additional analyses in experiment 4. Changes in body weight of the rats used TH588 hydrochloride in experiments 1C4 were assessed independently for each experiment with the use of two-way repeated measures ANOVAs with the week as the repeated factor and treatment as the between-subjects factor. Results Experiment 1 For sibutramine dataset, a parsimonious model for lard and chow consumption was used (Table?1; Fig.?1a). Throughout the observation period, animals consumed more lard than chow (Valuevalues denote significant effects aLard was used as the reference bVehicle was used as the reference cPost-treatment phase was used as the reference Open in a separate window Fig.?1 2-h consumption of lard and chow at baseline, during repeated treatment with sibutramine (a), memantine (b) or MTEP (c), and during post-treatment phase. The group means, the GEE-fitted lines, and the value for between-group differences (medication vs. vehicle control) are shown. Number of animals in each group Valuevalues denote significant effects aMemantine was used as the reference bPost-treatment phase was used as the reference For Lard, memantine decreased overall consumption (Valuevalues denote significant effects aMTEP was used as the reference bPost-treatment phase was used as the reference Animals treated with MTEP consumed less lard, but this effect was not significant (and for vehicle, sibutramine, memantine and MTEP, respectively. Number of animals in each group was 12C13 Table?4 Experiment 4 GEE score statistics with food consumption (kcal/kg b.w.) as outcome variable in four groups of animals with unlimited access to chow Value1C3 represents rats that were offered a limited access to the lard since the beginning of the TH588 hydrochloride experiment and were treated with respective medications during the treatment phase. represents rats that had continuous access to chow Rabbit polyclonal to ZNF146 but no access to lard Animals used in Experiment 4 were never offered the lard, and.