O'Hare E., Levine A.S., Semotuk M.T., Tierney K.J., Shephard R.A., Grace M.K., Cleary J.
Department of Psychiatry, University of Minnesota; Veterans Affairs Medical Center, Minneapolis, USA.
Behav Pharmacol. 1996 Dec;7(8):742-753.
The cyclic-ratio schedule methodology exposes animals to an ascending followed by a descending sequence of ratio values over six consecutive cycles. The response functions, obtained by plotting response rates against reinforcement rates at each schedule value, are argued to provide features useful in the evaluation of drug effects on feeding behavior. In the present study the effects of s.c. insulin (5.0IU/kg), i.c.v. neuropeptide Y (NPY) (5.0µg/5.0µl), i.c.v. insulin (0.5mU/5.0µl), i.c.v. 2-deoxyglucose (2-DG) (10.0µg/5.0µl), i.c.v. naloxone (NLX) (50.0µg/5.0µl) in conjunction with i.c.v. NPY (5.0µg/5.0µl), and i.c.v. NLX alone (50.0µg/5.0µl) were assessed, i.c.v. NPY, insulin and 2-DG caused an elevation of the response function obtained by plotting response rates against reinforcement rates but did not affect the slope of the function. This elevation was similar to that observed after increasing the incentive value of the reinforcer (i.e., similar to increasing a 5.0% sucrose concentration reinforcer to 10.0%, and to substituting 45mg sweet food pellets for 45mg grain pellets). S.c. insulin produced no shift in the function from baseline, and i.c.v. NLX blocked the effect of i.c.v. NPY. I.c.v. NLX given alone reduced the slope of the response function, by selectively reducing response rates at the higher schedule values, a shift in the function similar to that observed following an increase in body weight. Since the literature on NPY and insulin would suggest that their effects are mediated through mechanisms associated with internal regulation, these findings were not predicted.
循环比率时间表方法让动物在六个连续周期中先接触递增然后递减的比率值序列。通过在每个时间表值下绘制反应率与强化率的关系而获得的反应函数,被认为能提供有助于评估药物对进食行为影响的特征。在本研究中,评估了皮下注射胰岛素(5.0IU/kg)、脑室内注射神经肽Y(NPY)(5.0μg/5.0μl)、脑室内注射胰岛素(0.5mU/5.0μl)、脑室内注射2-脱氧葡萄糖(2-DG)(10.0μg/5.0μl)、脑室内注射纳洛酮(NLX)(50.0μg/5.0μl)联合脑室内注射NPY(5.0μg/5.0μl)以及单独脑室内注射NLX(50.0μg/5.0μl)的效果。脑室内注射NPY、胰岛素和2-DG导致通过绘制反应率与强化率关系而获得的反应函数升高,但不影响该函数的斜率。这种升高类似于在增加强化物的激励值后观察到的情况(即类似于将5.0%的蔗糖浓度强化物增加到10.0%,以及用45mg甜味食物颗粒替代45mg谷物颗粒)。皮下注射胰岛素未使函数从基线发生偏移,脑室内注射NLX阻断了脑室内注射NPY的效果。单独给予脑室内注射NLX通过选择性降低较高时间表值下的反应率而降低了反应函数的斜率,这种函数偏移类似于体重增加后观察到的情况。由于关于NPY和胰岛素的文献表明它们的作用是通过与内部调节相关的机制介导的,所以这些发现是无法预测的。