AVERSIVE PROPERTIES OF THE KAPPA-OPIOID AGONIST U50,488 IN THE WEEK-OLD RAT PUP
AVERSIVE PROPERTIES OF THE KAPPA-OPIOID AGONIST U50,488 IN THE WEEK-OLD RAT PUP
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DOI：
10.1007/bf02245218
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发表时间：
1994-01-01
影响因子：
3.4
通讯作者：
CARDEN, S
中科院分区：
文献类型：
--
作者：
BARR, GA;WANG, SN;CARDEN, S
mu 阿片类药物已被证明可以在大鼠出生后的第一周内产生镇痛作用并增强镇痛效果。卡帕阿片类药物对婴儿和成人也有镇痛作用，但对成熟动物可能会产生厌恶作用。我们通过三种方式检查了卡帕阿片受体激动剂 U50,488 在出生后第一周对幼鼠的厌恶作用。在第一个实验中，外周注射的 U50,488（1.0-30.0 mg/kg）与一种气味配对，8 小时后测试幼崽的位置偏好，以避免该气味。此任务类似于对成年动物使用的条件偏好/厌恶测试。在两个较高剂量的剂量下，3 天和 7 天大的幼崽都学会了避开有气味的掺假面。当暴露于之前与 U50,488 相关的气味时，两个年龄段的幼崽的运动活动都会减少。在第二个实验中，U50,488 的急性治疗在 3 天和 7 天时同样增加了超声波遇险发声 (USV)，增加了运动活动，并降低了直肠温度。后两种效应均与 USV 产量的增加无关。第三个实验表明，条件性气味提示在 3 日龄和 7 日龄幼犬中 8 小时后以 1.0-10.0 mg/kg 浓度增加 USV，而活动或直肠温度没有变化。这些研究的结果表明，U50,488 可以在新生大鼠幼崽中产生厌恶情绪，就像在成年大鼠中一样。
mu Opioids have been shown to produce analgesia and to be reinforcing during the first week of life in the rat. kappa Opioids also have analgesic actions in both the infant and adult, but can be aversive in the mature animal. We examined the aversive effects of the kappa opioid agonist U50,488 during the first postnatal week in the rat pup in three ways. In the first experiment, U50,488, injected peripherally (1.0-30.0 mg/kg), was paired with an odor and pups were tested 8 h later for positional preference for avoidance of that odor. This task is similar to conditioned preference/aversion tests used with adult animals. Both 3- and 7-day-old pups learned to avoid the odor adulterated side at the two higher doses. When exposed to odors previously associated with U50,488, pups at both ages decreased locomotor activity. In a second experiment, acute treatment with U50,488 increased ultrasonic distress vocalizations (USV) equally at 3 and 7 days of age, increased locomotor activity, and decreased rectal temperature. Neither of the latter two effects was correlated with the increase in USV production. The third experiment showed that conditioned odor cues increased USV 8 h later in 3- and 7-day-old pups at 1.0-10.0 mg/kg without changes in activity or rectal temperature. The results from these studies suggest that U50,488 can produce aversions in the neonatal rat pup as it does in the adult.