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

We recently reported that the oligosomatostatin receptor agonist, ODT8-SST increases food intake in rats via the somatostatin 2 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 1 μg/mouse) injected icv under short inhalation anesthesia dose-dependently increased cumulative light phase food intake over 4 h compared to vehicle with a 3.1-times increase at 1 μg/mouse (p < 0.05). Likewise, the sst2,3,5 agonist octreotide (0.3 or 1 μg/mouse) dose-dependently increased 4-h food intake, whereas selective sst1 or sst4 agonists at 1 μg/mouse did not. In vehicle-treated mice, high fat diet increased caloric intake/4 h by 2.8-times compared to regular diet (p < 0.05) and values were further increased 1.4-times/4 h 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 4 h 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 the activation of brain sst2 receptors potently stimulates the light phase 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.

Research Highlights
► A somatostatin 2 receptor (sst2) agonist icv increased food intake (fi) in mice.
► Also, octreotide increased fi but sst1 or sst4 agonists did not.
► Meal frequency was increased, inter-meal interval reduced but meal sizes not altered.
► Brain activation of sst2 receptors potently stimulates ingestive behavior.
► The sst2 agonist has an inhibitory effect on satiety but satiation is not altered.