De Vry J, Schreiber R, Daschke A, Jentzsch K R
CNS Research, Bayer AG, Aprather Weg 18a, D-42096 Wuppertal, Germany.
Eur Neuropsychopharmacol. 2003 Oct;13(5):337-45. doi: 10.1016/s0924-977x(03)00014-2.
Hypophagic effects of serotonergic drugs have mostly been investigated in free-feeding paradigms and are generally ascribed to drug-induced acceleration of satiety, or to behavioral disruption. The present study investigated the hypophagic effects of various 5-HT(1/2) receptor agonists in an operant paradigm. Because of its limited duration (10-min session) the procedure was considered to be relatively insensitive to satiety processes. The behavioral specificity of the hypophagic effect was assessed by additional testing of the compounds in a locomotor activity assay. Male Wistar rats, maintained at about 80% of their free-feeding weights, were trained to acquire stable operant responding in daily fixed ratio:10 food-reinforced sessions; after which they were tested once a week with a 5-HT receptor agonist. Each compound dose-dependently suppressed the number of earned pellets after i.p. administration: DOI (5-HT(2A/2C) receptor agonist; ED(50): 0.36 mg/kg), TFMPP (5-HT(1B/2C/2A); 0.37 mg/kg), m-CPP (5-HT(2C/1B/2A); 0.54 mg/kg), ORG 37684 (5-HT(2C/2A); 0.85 mg/kg), CP-94,253 (5-HT(1B); 2.09 mg/kg), BW 723C86 (5-HT(2B); 6.26 mg/kg) and ipsapirone (5-HT(1A); 10.17 mg/kg). When tested at the dose equivalent to the ED(50) value in the operant paradigm, only ORG 37684 and DOI weakly suppressed activity counts in a locomotor activity assay; suggesting that the inhibition of operant food intake obtained with the other compounds at these doses is not a direct consequence of unconditioned motor effects. It is suggested that the hypophagic effect induced by relatively low doses of CP-94,253, TFMPP and m-CPP, and by moderate doses of ipsapirone and BW 723C86, is partly due to a drug-induced suppression of appetite. Although the exact contribution of the diverse 5-HT(1/2) receptor subtypes to appetite control remains to be studied in more detail, it is hypothesized that activation of 5-HT(1B) and/or 5-HT(2C) receptors attenuates appetite.
血清素能药物的食欲减退作用大多是在自由进食模式下进行研究的，通常归因于药物诱导的饱腹感加速或行为干扰。本研究在操作性范式中研究了各种5-HT(1/2)受体激动剂的食欲减退作用。由于其持续时间有限（10分钟时段），该程序被认为对饱腹感过程相对不敏感。通过在运动活动测定中对化合物进行额外测试来评估食欲减退作用的行为特异性。维持体重约为自由进食体重80%的雄性Wistar大鼠，经过训练以在每日固定比率：10次食物强化时段中获得稳定的操作性反应；之后每周用一种5-HT受体激动剂对它们进行一次测试。每种化合物腹腔注射后均剂量依赖性地抑制获得的食丸数量：DOI（5-HT(2A/2C)受体激动剂；ED(50)：0.36毫克/千克）、TFMPP（5-HT(1B/2C/2A)；0.37毫克/千克）、m-CPP（5-HT(2C/1B/2A)；0.54毫克/千克）、ORG 37684（5-HT(2C/2A)；0.85毫克/千克）、CP-94,253（5-HT(1B)；2.09毫克/千克）、BW 723C86（5-HT(2B)；6.26毫克/千克）和伊沙匹隆（5-HT(1A)；10.17毫克/千克）。当在操作性范式中以相当于ED(50)值的剂量进行测试时，只有ORG 37684和DOI在运动活动测定中微弱地抑制活动计数；这表明在这些剂量下用其他化合物获得的操作性食物摄入量的抑制不是无条件运动效应的直接结果。有人提出，相对低剂量的CP-94,253、TFMPP和m-CPP以及中等剂量的伊沙匹隆和BW 723C86诱导的食欲减退作用部分是由于药物诱导的食欲抑制。尽管不同的5-HT(1/2)受体亚型对食欲控制的确切贡献仍有待更详细地研究，但据推测5-HT(1B)和/或5-HT(2C)受体的激活会减弱食欲。
