Collins R L, Zavala A R, Ingersoll V Y, Duke M A, Crawford C A, McDougall S A
Department of Psychology, California State University, San Bernardino 92407, USA.
Psychopharmacology (Berl). 1998 Jun;137(3):282-91. doi: 10.1007/s002130050621.
When given acutely, drugs that stimulate kappa opioid receptors (e.g., U-50,488) enhance the locomotor activity of preweanling rats and induce regional increases in Fos immunoreactivity (IR). In contrast, the effects of chronic treatment with kappa opioid agonists are unknown. The purpose of the present study was two-fold: first, to determine whether repeated treatment with a kappa opioid agonist would sensitize the locomotor activity of preweanling rats and, second, to determine whether changes in Fos IR correspond with the occurrence of locomotor sensitization. To test these hypotheses, rats were injected with U-50,488 (5 mg/kg, s.c.) or saline on either postnatal days (PD) 5-9 or PD 11-15. For rats pretreated on PD 5-9, a test day injection of U-50,488 or saline was given after either 1 or 7 abstinence days (i.e., at PD 11 or PD 17). For rats pretreated on PD 11-15, a test day injection of U-50,488 or saline was given after 1 abstinence day (i.e., at PD 17). In two additional experiments, the acute and chronic effects of U-50,488 treatment were assessed in adult rats. As expected, repeated treatment with U-50,488 produced locomotor sensitization at both PD 11 and PD 17, but only when the test day occurred 1, and not 7, days after cessation of drug pretreatment. Thus, the persistence of the sensitized response was very brief. Test day treatment with U-50,488 stimulated Fos IR in various brain regions of the preweanling rat, including the medial striatum, nucleus accumbens, lateral habenula, and septal area. Chronic treatment with U-50,488 depressed Fos expression in a number of brain regions (relative to acutely treated rats); however, these changes in Fos IR did not necessarily coincide with the occurrence of behavioral sensitization. Repeated treatment with U-50,488 did not produce locomotor sensitization in adult rats, so Fos IR was not assessed in this age group. Therefore, while acute treatment with U-50,488 both increased locomotor activity and stimulated Fos IR in preweanling rats, chronic U-50,488 treatment produced behavioral changes that did not correspond with Fos expression.
急性给予刺激κ阿片受体的药物（如U - 50,488）时，可增强断奶前大鼠的运动活性，并诱导Fos免疫反应性（IR）在局部区域增加。相比之下，κ阿片激动剂慢性治疗的效果尚不清楚。本研究的目的有两个：第一，确定用κ阿片激动剂重复治疗是否会使断奶前大鼠的运动活性敏感化；第二，确定Fos IR的变化是否与运动敏感化的发生相对应。为了验证这些假设，在出生后第（PD）5 - 9天或PD 11 - 15天给大鼠注射U - 50,488（5mg/kg，皮下注射）或生理盐水。对于在PD 5 - 9预处理的大鼠，在禁食1天或7天后（即PD 11或PD 17）给予试验日注射U - 50,488或生理盐水。对于在PD 11 - 15预处理的大鼠，在禁食1天后（即PD 17）给予试验日注射U - 50,488或生理盐水。在另外两个实验中，评估了U - 50,488治疗对成年大鼠的急性和慢性影响。正如预期的那样，用U - 50,488重复治疗在PD 11和PD 17均产生了运动敏感化，但仅当试验日在药物预处理停止后1天而非7天时出现。因此，敏感化反应的持续时间非常短暂。试验日用U - 50,488治疗可刺激断奶前大鼠不同脑区的Fos IR，包括内侧纹状体、伏隔核外侧缰核和隔区。用U - 50,488慢性治疗会使多个脑区的Fos表达降低（相对于急性治疗的大鼠）；然而，Fos IR的这些变化不一定与行为敏感化的发生一致。用U - 50,488重复治疗在成年大鼠中未产生运动敏感化，因此未在该年龄组中评估Fos IR。因此，虽然急性给予U - 50,488可增加断奶前大鼠的运动活性并刺激Fos IR，但慢性给予U - 50,488产生的行为变化与Fos表达不对应。
