Effects of the kappa-opioid receptor agonist U-50,488 on morphine-induced place preference conditioning in the developing rat
Effects of the kappa-opioid receptor agonist U-50,488 on morphine-induced place preference conditioning in the developing rat
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DOI：
10.1016/s0014-2999(96)00698-x
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发表时间：
1996-12-12
影响因子：
5
通讯作者：
McDougall, SA
中科院分区：
文献类型：
--
作者：
Bolanos, CA;Garmsen, GM;McDougall, SA
利用条件位置偏好范式，在断奶前（10日龄和12日龄）和青春期前后（35日龄）大鼠中评估了kappa-阿片受体激动剂反式-(+/-)-3,4-二氯- n -甲基- n -[2-（1-吡咯烷基）-环己基]-苯乙酰胺甲磺酸（U-50,488）调节吗啡诱导奖励的能力。条件反射和测试是在一个有三个隔间的房间里进行的，每个隔间都有自己独特的触觉和气味线索（杏仁或柠檬）。采用一种简化的条件位置偏好程序，在第一天给予大鼠两组盐气味配对，第二天给予大鼠两组盐或吗啡气味配对。在一些实验中，给大鼠注射U-50,488 （2-10 mg/kg, s.c）。30min前给予吗啡（0.1- 8mg /kg, ig）。第三天，允许大鼠自由进入整个900 s的房间，并确定隔间偏好。与成年大鼠相似，吗啡（0.5 mg/kg）在两个断奶前年龄组中始终能够诱导条件位置偏好。这一作用被k -阿片受体激动剂预处理减弱，因为U-50,488不仅增强了10和17日龄大鼠的运动活性，而且阻断了吗啡诱导的幼龄动物的位置偏好条件反射。相比之下，青春期前后（35天大）的大鼠没有表现出吗啡诱导的位置偏好，也没有在U-50,488治疗后表现出增强的运动活动；然而，使用相同的程序，另一组年龄相似的大鼠表现出20 mg/kg可卡因（i.p.）产生的条件偏好。因此，这些结果表明，在断奶前大鼠（至少在10天大），奖励过程在功能上是成熟的，但青春期周围的大鼠通常对mu-和kappa-阿片类药物没有反应。
The ability of the kappa-opioid receptor agonist trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide methanesulfonate (U-50,488) to modulate morphine-induced reward was assessed in preweanling (10- and Iri-day-old) and periadolescent (35-day-old) rats using the conditioned place preference paradigm. Conditioning and testing were conducted in a three compartment chamber, with each end compartment having its own distinct tactile and odor cues (almond or lemon). An abbreviated conditioned place preference procedure was used in which rats received two saline-odor pairings on the first conditioning day, and two saline- or morphine-odor pairings on the second day. In some experiments, rats were given U-50,488 (2-10 mg/kg, s.c.) 30 min prior to bring conditioned with morphine (0.1-8 mg/kg, i.p.). On the third day, rats were allowed free access to the entire chamber fur 900 s and compartment preferences were determined. Similar to adult rats, morphine (0.5 mg/kg) was consistently able to induce conditioned place preferences in the two preweanling age groups. This effect was attenuated by K-opioid receptor agonist pretreatment, as U-50,488 not only enhanced the locomotor activity of 10- and 17-day-old rats, but it blocked the morphine-induced place preference conditioning of these younger animals. In contrast, periadolescent (35-day-old) rats did not exhibit morphine-induced place preferences, nor did they show enhanced locomotor activity after U-50,488 treatment; however, using the same procedure, a different group of similarly aged rats showed conditioned preference produced by 20 mg/kg cocaine (i.p.). Therefore, these results suggest that reward processes are functionally mature in the preweanling rat (at least by 10 days of age), but that periadolescent rats an generally unresponsive to mu- and kappa-opioid drugs.