Orexigenic response to tail pinch: role of brain NPY(1) and corticotropin releasing factor receptors.

Tail pinch stimulates food intake in rats. We investigated brain mechanisms of this response and the influence of repeated exposure. Sprague-Dawley rats received acute (5 min) or repeated (5 min/day for 14 days) tail pinch using a padded clip. Acute tail pinch increased 5-min food intake compared with control (0.92 ± 0.2 vs. 0.03 ± 0.01 g, P < 0.01). This response was inhibited by 76% by intracerebroventricular injection of BIBP-3226, a neuropeptide Y1 (NPY1) receptor antagonist, increased by 48% by astressin-B, a corticotropin-releasing factor (CRF) receptor antagonist, and not modified by S-406-028, a somatostatin subtype 2 antagonist. After the 5-min tail pinch without food, blood glucose rose by 21% (P < 0.01) while changes in plasma acyl ghrelin (+41%) and adrenocorticotropic hormone (+37%) were not significant. Two tail pinches (45 min apart) activate pontine and hindbrain catecholaminergic and hypothalamic paraventricular CRF neurons. After 14 days of repeated tail pinch, the 5-min orexigenic response was not significantly different from days 2 to 11 but reduced by 50% thereafter (P < 0.001). Simultaneously, the 5-min fecal pellet output increased during the last 5 days compared with the first 5 days (+58%, P < 0.05). At day 14, the body weight gain was reduced by 22%, with a 99% inhibition of fat gain and a 25% reduction in lean mass (P < 0.05). The orexigenic response to acute 5-min tail pinch is likely to involve the activation of brain NPY1 signaling, whereas that of CRF tends to dampen the acute response and may contribute to increased defecation and decreased body weight gain induced by repeated tail pinch.