Dourish C T, Hutson P H, Kennett G A, Curzon G
Appetite. 1986;7 Suppl:127-40. doi: 10.1016/s0195-6663(86)80058-7.
The pharmacological and neurochemical bases of hyperphagia induced by the serotonin agonist 8-OH-DPAT were examined. In addition, the possible therapeutic potential of 8-OH-DPAT and related drugs in the treatment of anorexic pathology was assessed in an animal model of anorexia (as induced by acute immobilization stress). In normal rats 8-OH-DPAT elicited feeding after peripheral injection and after intracerebral application to the brainstem raphé nuclei. Feeding elicited by peripheral injection of the drug was attenuated by pretreatment with the serotonin synthesis inhibitor para-chlorophenylalanine. Following a hyperphagic dose of 8-OH-DPAT, brain serotonin metabolism was reduced, particularly in midbrain and pons-medulla. Our interpretation of these data is that 8-OH-DPAT elicits feeding via an agonist action on serotonin autoreceptors in the raphé nuclei. These receptors are probably of the 5-HT1A subtype as 8-OH-DPAT has a high affinity for this receptor and other putative 5-HT1A agonist (i.e. buspirone, TVX Q 7821) also elicit feeding. In contrast, putative 5-HT1B agonists (i.e. RU-24969 and quipazine) decrease feeding and cause anorexia. 8-OH-DPAT and other 5-HT1A agonists attenuated the anorexia and body weight loss caused by immobilization stress. Therefore, it seems possible that 5-HT1A agonists may be clinically useful in the treatment of anorexia.
研究了血清素激动剂8-OH-DPAT诱导的食欲亢进的药理学和神经化学基础。此外，在厌食症动物模型（由急性固定应激诱导）中评估了8-OH-DPAT及相关药物在治疗厌食症病理方面的潜在治疗潜力。在正常大鼠中，外周注射8-OH-DPAT后以及将其脑内应用于脑干中缝核后均引发进食。血清素合成抑制剂对氯苯丙氨酸预处理可减弱药物外周注射引发的进食。给予8-OH-DPAT促食欲剂量后，脑内血清素代谢降低，尤其是在中脑和脑桥-延髓。我们对这些数据的解释是，8-OH-DPAT通过对中缝核中血清素自身受体的激动作用引发进食。这些受体可能是5-HT1A亚型，因为8-OH-DPAT对该受体具有高亲和力，并且其他假定的5-HT1A激动剂（即丁螺环酮、TVX Q 7821）也引发进食。相比之下，假定的5-HT1B激动剂（即RU-24969和喹哌嗪）减少进食并导致厌食。8-OH-DPAT和其他5-HT1A激动剂减轻了固定应激引起的厌食和体重减轻。因此，5-HT1A激动剂在临床上可能对治疗厌食症有用。
