Activation of brain somatostatin 2 receptors stimulates feeding in mice: Analysis of food intake microstructure

Abstract

We recently reported that the oligosomatostatin receptor agonist, ODT8-SST increases food intake in rats via the somatostatin2 receptor (sst2). We characterized ingestive behavior following intracerebroventricular (icv) injection of a selective sst2 agonist in freely fed mice during the light phase. The sst2 agonist (0.01, 0.03, 0.1, 0.3 or 1µg/mouse) injected icv under short inhalation anesthesia dose-dependently increased cumulative light phase food intake over 4h compared to vehicle with a 3.1-times increase at 1µg/mouse (p<0.05). Likewise, the sst2,3,5 agonist octreotide (0.3 or 1µg/mouse) dose-dependently increased 4-h food intake, whereas selective sst1 or sst4 agonists at 1µg/mouse did not. In vehicle-treated mice, high fat diet increased caloric intake/4h by 2.8-times compared to regular diet (p<0.05) and values were further increased 1.4-times/4h by the sst2 agonist. Automated continuous assessment of food intake established a 6.6-times higher food intake during the dark phase due to increased number of meals, meal size, meal duration and rate of ingestion compared to non-treated mice during the light phase. During the first 4h post icv sst2 agonist injection, mice had a 57% increase in number of meals with a 60% higher rate of ingestion, and a 61% reduction in inter-meal intervals, whereas meal sizes were not altered compared to vehicle. These data indicate that activation of brain sst2 receptors potently stimulates ingestive behavior under basal or high fat diet-stimulated conditions in mice. The shortened inter-meal interval suggests an inhibitory effect of the sst2 agonist on “satiety”, whereas “satiation” is not altered as indicated by normal meal size.

Differences in Regional Brain Responses to Food Ingestion After Roux-en-Y Gastric Bypass and the Role of Gut Peptides: A Neuroimaging Study

“…There may be differences in the effects of octreotide and somatostatin. Octreotide may have a direct action on the brain (36). However, Goldstone et al (7) found no direct effect of octreotide on food reward behaviors in NW subjects or, when given with insulin, on postprandial hunger or fullness after RYGB.…”

CCK-8 and CCK-58 differ in their effects on nocturnal solid meal pattern in undisturbed rats

“…We have previously established the automated system in mice and shown the same food intake, as observed manually during the light and dark phase (52). Because these data were generated in a different species, we performed an additional experiment in rats to validate automated vs. manual measurement of dark-phase food intake.…”

“…Food intake pattern was assessed as established in our previous studies (21,52) using an automated episodic food intake-monitoring system for regular pellet rat food (BioDAQ, Research Diets, New Brunswick, NJ). Water was provided ad libitum from regular water bottles.…”

“…Because the analysis of the feeding microstructure is essential to assess the mechanisms regulating feeding behavior (18), we investigated the feeding pattern using a newly developed automated episodic food intake-monitoring device, which allows the undisturbed continuous monitoring during the dark phase with minimal human interference. This has been used in rats before (15,31,39,49) and was established recently for the use in mice (21,52). To investigate the specificity of the observed effects on feeding behavior, other behavioral parameters, such as grooming and locomotor activity, were assessed as established originally by Antin et al (1) and in our previous studies (50,53).…”

PACAP intraperitoneal treatment suppresses appetite and food intake via PAC1 receptor in mice by inhibiting ghrelin and increasing GLP-1 and leptin

“…Microstructure analysis of food intake was performed using the BioDAQ episodic food intake monitor for mice (Research Diets, New Brunswick, NJ). This system allows the continuous monitoring of meal patterns in undisturbed mice with minimal human interference as described in previously published studies (49). The system weighs the food hopper (Ϯ0.01 g) second by second and detects not eating as weight stable, and eating as weight unstable.…”