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

23 24 Goebel-Stengel M, Stengel A, Wang L, Taché Y. Orexigenic response to tail pinch: role of 25 brain NPY1 and corticotropin releasing factor receptors. Am J Physiol Regul Integr Comp Physiol 26 Tail pinch stimulates food intake in rats. We investigated brain mechanisms of this response and 27 the influence of repeated exposure. Sprague-Dawley rats received acute (5 min) or repeated (5 28 min/day for 14 days) tail pinch using a padded clip. Acute tail pinch increased 5-min food intake 29 compared to control (0.92 ± 0.2 vs. 0.03 ± 0.01 g, P<0.01). This response was inhibited by 76% 30 by intracerebroventricular injection of BIBP-3226, a neuropeptide Y1, (NPY1) antagonist, 31 increased by 48% by astressin-B, a corticotropin releasing factor (CRF) antagonist and not 32 modified by S-406-028, a somatostatin subtype 2 antagonist. After the 5-min tail pinch without 33 food, blood glucose rose by 21% (P<0.01) while changes in plasma acyl ghrelin (+41%) and 34 ACTH (+37%) were not significant. Two tail pinches (45 min apart) activate pontine and 35 hindbrain catecholaminergic and hypothalamic paraventricular CRF neurons. After 14 days 36 repeated tail pinch, the 5-min orexigenic response was not significantly different from days 2-11 37 but reduced by 50% thereafter (P<0.001). Simultaneously, the 5-min fecal pellet output increased 38 during the last 5 days compared to the first 5 days (+58%, P<0.05). At day 14, the body weight 39 gain was reduced by 22%, with a 99% inhibition of fat gain and a 25% reduction in lean mass 40 (P<0.05). The orexigenic response to acute 5-min tail pinch is likely to involve activation of 41 brain NPY1 signaling while that of CRF tends to dampen the acute response and may contribute 42 to increased defecation and decreased body weight gain induced by repeated tail pinch. 43 44