Kow L M, Tsai Y F, Wang L, Pfaff D W
Rockefeller University, New York, NY 10021-6399.
Chin J Physiol. 1992;35(2):105-21.
Previously, we have shown that serotonin (5-HT) can inhibit, excite, or biphasically inhibit and excite individual neurons of the ventromedial nucleus (VMN) in hypothalamic slices from female rats. In the present study, similar in vitro methods were used to further characterize VMN neurons responsive to 5-HT, and to identify the receptor subtypes involved in mediating these 5-HT actions. Results from a dose-response experiment indicate that increasing the dose of 5-HT can transform an inhibitory response into a biphasic or even an excitatory response. This indicates that modulation of 5-HT release in the VMN could alter the net response of the VMN to this transmitter. By comparing the actions of 5-HT with the effects of selective agonists and antagonists, the inhibitory action was found to be mediated predominantly, if not exclusively, by 5-HT1A receptors, while the excitatory action was mediated predominantly or exclusively through 5-HT2 receptors. There appear to be few, if any, 5-HT3 receptors in the VMN, and their functions are unclear. The inhibitory and the excitatory phases of the biphasic responses were not mediated together by a single receptor subtype but were mediated separately by 5-HT1A and 5-HT2 receptors, respectively. The presence of the biphasic response in a large proportion of neurons, therefore, indicates the coexistence of different subtypes of 5-HT receptors in many individual VMN neurons. The use of selective agonists and antagonists further indicates that the coexistence also occurs in neurons showing monophasic responses, and that the opposite actions mediated by the coexisting receptor subtypes can interact with each other. Therefore, changing the ratio of coexisting receptor subtypes could modify the net output of the VMN response to 5-HT. Together with behavioral studies by others, it emerges from our findings that the inhibitory action of 5-HT on VMN neurons is associated with, and may be responsible for, the stimulation of feeding and inhibition of lordosis, while the excitatory action is related and may lead to the opposite behavioral effects. Finally, with the coexistence in VMN neurons of two receptor subtypes that can mediate 5-HT effects on both feeding and lordosis, the VMN can serve as a substrate for 5-HT to coordinate these two behaviors.
此前，我们已经表明，血清素（5-羟色胺，5-HT）可以抑制、兴奋，或双相抑制并兴奋来自雌性大鼠下丘脑切片腹内侧核（VMN）的单个神经元。在本研究中，我们采用了类似的体外方法，以进一步表征对5-HT有反应的VMN神经元，并确定介导这些5-HT作用的受体亚型。剂量反应实验的结果表明，增加5-HT的剂量可以将抑制反应转变为双相甚至兴奋反应。这表明VMN中5-HT释放的调节可能会改变VMN对这种神经递质的净反应。通过比较5-HT的作用与选择性激动剂和拮抗剂的效果，发现抑制作用主要（如果不是唯一）由5-HT1A受体介导，而兴奋作用主要或完全通过5-HT2受体介导。VMN中似乎几乎没有（如果有的话）5-HT3受体，其功能尚不清楚。双相反应的抑制和兴奋阶段不是由单一受体亚型共同介导的，而是分别由5-HT1A和5-HT2受体介导的。因此，在大部分神经元中存在双相反应，表明许多单个VMN神经元中存在不同亚型的5-HT受体。选择性激动剂和拮抗剂的使用进一步表明，共存也发生在表现为单相反应的神经元中，并且共存受体亚型介导的相反作用可以相互作用。因此，改变共存受体亚型的比例可能会改变VMN对5-HT反应的净输出。结合其他人的行为研究，我们的研究结果表明，5-HT对VMN神经元的抑制作用与进食刺激和脊柱前凸抑制有关，并且可能是其原因，而兴奋作用则与之相关，可能导致相反的行为效应。最后，由于VMN神经元中存在两种可以介导5-HT对进食和脊柱前凸作用的受体亚型，VMN可以作为5-HT协调这两种行为的基础。
