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. 2017 Sep 12;23(5):1157–1168. doi: 10.1038/mp.2017.187

Figure 2.

Figure 2

Behavioral and molecular consequences of glucagon-like peptide-1 receptor (GLP-1R) activation in the lateral hypothalamus (LH), as well as their interactions with the estrous cycle, in female rats. In females only the higher dose of exendin-4 (Ex4) reduced the amount of sucrose rewards earned (a) and resulted in a trend to reduce the number of lever presses for the rewards (b) in a progressive ratio schedule, without changing activity at the inactive lever (c). Food ingestion was also affected in female rats but only by the higher dose of Ex4, as illustrated by a reduction in 1 (d) and 24 h (e) chow intake (n=9–37). LH GLP-1R activation in females has divergent behavioral and molecular impact in different estrus cycle phases. Intra-LH Ex4 reduced the effort to obtain a reward (f–i) in a sucrose-motivated progressive ratio task in females in the estrus phase (E) but not metestrus or diestrus (MD) phase of their cycle. Performance on the inactive lever or locomotor activity during the task was not altered by Ex4 in any of the cycle phases (j–m). Although Ex4 potently reduced ingestive behavior in all females irrespective of the cycle phase, the reduction was enhanced for females in E (n–q). Data are expressed as mean±s.e.m. For each measured parameter, raw values and values calculated as the percentage of vehicle response are presented in order to minimize the impact of baseline differences across the two cycle groups. n=10–11. Behavioral differences were mirrored by similarly divergent gene expression changes induced by intra-LH Ex4 application, where a potent induction of interleukins was only detected in females in E, and a reduction in orexin or neurotensin expression was only present in E (r). A reduced expression of melanin-concentrating hormone (MCH) was the only mRNA change preserved in MD phases. Data were normalized to the housekeeping gene beta-actin and are expressed as mean±s.e.m. n=19: vehicle in E, n=20: Ex4 in E, n=8: vehicle in MD, n=8: Ex4 in MD. *P<0.05, **P<0.01,***P<0.001, ****P<0.0001.