Winslow J T, Insel T R
National Institute of Mental Health, Poolesville, Maryland 20837.
Behav Neurosci. 1991 Apr;105(2):253-63. doi: 10.1037//0735-7044.105.2.253.
Previous studies with several different species have suggested that opioids and their receptors are involved in the mediation of the infant's vocal response to social isolation. In the case of the rat pup, 2 models have been hypothesized to relate opioids and the ultrasonic call emitted during social isolation. One model views the comforting effects of social contact as opioid mediated and the apparent distress of social isolation as analogous to opiate withdrawal. The 2nd model considers social separation as a stressor that recruits endogenous opioids. This article describes 3 experiments that tested both of these models in 7-10-day-old rat pups. In Experiment 1, morphine (0.04-0.40 mg/kg) decreased the rate of isolation calls in a dose-dependent, naloxone-reversible fashion. However, the decrease in calling rate was observed only at doses that decreased locomotor activity. Administration of the reversible opiate antagonist naloxone (0.05-5.0 mg/kg) did not alter the rate of calls during either 2- or 6-min isolation tests at either 24 or 32 degrees C. In Experiment 2, the irreversible mu opioid receptor antagonist beta-funaltrexamine (beta-FNA) was administered into the lateral ventricle of 6-day-old pups. Again, no change in the rate of isolation calls was found, although sensitivity to morphine was markedly decreased, and mu (but not delta or kappa) receptors were decreased in selected brain regions by about 40%. In Experiment 3, in vivo receptor binding was used to directly investigate the availability of mu opioid receptors during social contact and social isolation. Pups injected with 3H-diprenorphine showed relatively high levels of specific in vivo binding that followed the regional pattern of in vitro binding, but no effects of social isolation were apparent in the 5 brain regions assayed. Taken together, the consistent negative results with opiate receptor antagonists, as well as the inability to detect an alteration of in vivo binding, suggest that the mu opioid receptor is not an essential part of the rat pup's vocal response to social separation.
此前针对几种不同物种开展的研究表明，阿片类药物及其受体参与介导婴儿对社会隔离的发声反应。就幼鼠而言，已提出两种模型来阐述阿片类药物与社会隔离期间发出的超声波叫声之间的关系。一种模型认为，社会接触的安抚作用是由阿片类药物介导的，而社会隔离时明显的痛苦类似于阿片类药物戒断反应。第二种模型则将社会隔离视为一种应激源，它会促使内源性阿片类药物的释放。本文描述了3项实验，这些实验在7至10日龄的幼鼠身上对这两种模型都进行了测试。在实验1中，吗啡（0.04 - 0.40毫克/千克）以剂量依赖性、纳洛酮可逆的方式降低了隔离叫声的发生率。然而，仅在降低运动活动的剂量下才观察到叫声发生率的降低。给予可逆性阿片类拮抗剂纳洛酮（0.05 - 5.0毫克/千克），在24或32摄氏度下进行的2分钟或6分钟隔离测试期间，均未改变叫声发生率。在实验2中，将不可逆的μ阿片受体拮抗剂β-芬太尼胺（β-FNA）注入6日龄幼鼠的侧脑室。同样，尽管对吗啡的敏感性显著降低，且选定脑区的μ（而非δ或κ）受体减少了约40%，但隔离叫声的发生率并未改变。在实验3中，采用体内受体结合法直接研究社会接触和社会隔离期间μ阿片受体的可利用性。注射了3H-二丙诺啡的幼鼠显示出相对较高水平的特异性体内结合，其遵循体外结合的区域模式，但在所检测的5个脑区中，未发现社会隔离有明显影响。综合来看，阿片受体拮抗剂始终得出阴性结果，以及无法检测到体内结合的改变，表明μ阿片受体并非幼鼠对社会隔离发声反应的必要组成部分。
