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Somatostatin and octreotide injected into the brain have been reported to modulate food intake. However, little is known regarding the underlying mechanisms. The stable oligosomatostatin analog, des-AA1,2,4,5,12,13-[DTrp8]-somatostatin (ODT8-SST), like somatostatin, binds to all five somatostatin receptors (sst1–5). We characterized the effects of ODT8-SST injected intracerebroventricularly (icv) on food consumption and related mechanisms of action in freely fed rats. ODT8-SST (0.3 and 1 μg per rat, icv) injected during the light or dark phase induced an early onset (within 1 h) and long-lasting (4 h) increase in food intake in nonfasted rats. By contrast, ip injection (0.3–3 mg/kg) or icv injection of selective sst1 or sst4 agonists (1 μg per rat) had no effect. The 2 h food intake response during the light phase was blocked by icv injection of a sst2 antagonist, the neuropeptide Y (NPY) Y1 receptor antagonist, BIBP-3226, and ip injection of the μ-opioid receptor antagonist, naloxone, and not associated with changes in plasma ghrelin levels. ODT8-SST (1 μg per rat, icv) stimulated gastric emptying of a solid meal which was also blocked by naloxone. The increased food intake was accompanied by a sustained increase in respiratory quotient, energy expenditure, and drinking as well as μ-opioid receptor-independent grooming behavior and hyperthermia, while ambulatory movements were not altered after ODT8-SST (1 μg per rat, icv). These data show that ODT8-SST acts primarily through brain sst2 receptors to induce a long-lasting orexigenic effect that involves the activation of Y1 and opiate-receptors, accompanied by enhanced gastric transit and energy expenditure suggesting a modulation of NPYergic and opioidergic orexigenic systems by brain sst2 receptors.

endocrinology

Central Injection of the Stable Somatostatin Analog ODT8-SST Induces a Somatostatin2 Receptor-Mediated Orexigenic Effect: Role of Neuropeptide Y and Opioid Signaling Pathways in Rats