The paraventricular hypothalamic nucleus is involved in exendin-4-induced emesis and inhibition of food and water intake in Suncus murinus

Abstract

<b>Introduction</b> Our previous studies using Suncus murinus demonstrated that the action of exendin-4 to induce emesis is mediated via GLP-1 receptors in the brainstem and/or hypothalamus; its anorectic action may involve similar brain areas and a “non-classical” GLP-1 receptor.

<b>Aims & Methods</b> In the present studies, we investigated if the emetic and anorectic effects of exendin-4 involve the paraventricular hypothalamic nucleus. The expression of GLP-1 immunoreactive neurons and GLP-1 receptors were measured using immunohistochemistry.

In functional studies, animals were anaesthetized with sodium pentobarbitone (40 mg/kg, i.p.) and then stereotaxically implanted with a guide cannula into the paraventricular hypothalamic nuclei and allowed a 7-days recovery before further experimentation. Animals were fasted 12 h prior to administration of exendin-4 (3 – 300 pmol, iPVH) or saline (1 µl, iPVH). Food and water consumption and behavior were measured for 1 hour.

<b>Results</b> GLP-1 immunoreactive neurons and receptors were detected in the paraventricular hypothalamic nucleus of S. murinus. In conscious, freely moving animals, iPVH administration of exendin-4 (3 – 30 pmol) inhibited significantly food and water intake in a dose-dependent manner (P <0.05; n = 4 – 6) without affecting the latency to feeding. Exendin-4 at 100 and 300 pmol, iPVH, induced emesis with 14.3 ± 3.7 and 23.3 ± 11.4 episodes, respectively, in all animals; the latency to the first episode varied between 4.1 and 83.5 min (P> 0.05). Exendin-4 at 100 and 300 pmol, iPVH, also prohibited food and water intake (P< 0.001).

<b>Conclusion</b> Our data suggests that the paraventricular hypothalamic nucleus mediates exendin-4-induced emesis and an inhibition of food and water intake in S. murinus. These studies were fully supported by a grant from the Research Grants Council of the Hong Kong SAR, China (Project no. UGC/FDS11/M02/15).