THE HEAD-TWITCH RESPONSE IN THE LEAST SHREW (CRYPTOTIS-PARVA) IS A 5-HT2-MEDIATED AND NOT A 5-HT1C-MEDIATED PHENOMENON
THE HEAD-TWITCH RESPONSE IN THE LEAST SHREW (CRYPTOTIS-PARVA) IS A 5-HT2-MEDIATED AND NOT A 5-HT1C-MEDIATED PHENOMENON
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DOI：
10.1016/0091-3057(94)90542-8
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发表时间：
1994-06-01
影响因子：
3.6
通讯作者：
GERDES, GF
中科院分区：
文献类型：
--
作者：
DARMANI, NA;MOCK, OB;GERDES, GF
我们的初步研究表明，5-HT2/ 1c激动剂(+/-)-1-(2,5-二甲氧基-4-碘苯基-2-氨基丙烷[(+/-)- doi]通过刺激5-HT2受体在小鼠中产生头抽搐反应（HTR）和抓耳反应（ESR）。然而，挑战研究表明，这些行为是通过两种不同的受体（可能是5-HT2和5-HT1C）产生的。由于缺乏选择性试剂，人们不能指定特定受体激活的特定反应。对(+/-)- doi比啮齿类动物更敏感的最小鼩鼱的这种行为是本研究的目的。在鼩鼱中IP注射(+/-)- doi产生了剂量依赖性（钟形）和时间依赖性的HTR频率增加。（+/-）- doi诱导的HTR被5-HT2/1C拮抗剂酮色林和spiperone等量完全减弱。具有5-HT2激动作用的5-HT1C拮抗剂lisuride也以钟形剂量和时间依赖性的方式产生HTR。中心注射(+/-)- doi （0.2 μ g）和lisuride （0.5 μ g）也能诱导行为。外周和中央给药利维脲均未能产生ESR。（+/-）- doi仅在最高剂量（2.5 mg/kg， IF）下显著诱导ESR。与车辆对照相比，中央管理的(+/-)- doi （0.2 μ g）产生了更多的esr；然而，这种差异并没有达到显著性。在低剂量（0.31和0.63 mg/kg）下，(+/-)- doi对运动活动没有影响，但在大剂量下显著减弱运动行为。低剂量和高剂量的lisuride都增加了运动活动。Spiperone剂量依赖性地抑制运动，而ketanserin没有作用。目前的结果表明，HTR是5-HT2受体介导的事件，运动活动的变化不影响HTR的诱导。
Our initial studies suggested that the 5-HT2/1C agonist(+/-)-1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane [(+/-)-DOI] produces both the head-twitch response (HTR) and the ear-scratch response (ESR) in mice via stimulation of 5-HT2 receptors. However, challenge studies revealed that these behaviors are produced via two different receptors (possibly 5-HT2 and 5-HT1C). Due to a lack of selective agents one cannot designate a particular response for the activation of a specific receptor. The purpose of the present study was to investigate such behaviors in the least shrew, which is more sensitive to (+/-)-DOI than rodents. IP injection of (+/-)-DOI in shrews produced a dose-dependent (bell-shaped) and time-dependent increase in the HTR frequency. The (+/-)-DOI-induced HTR was equipotently and completely attenuated by the 5-HT2/1C antagonists ketanserin and spiperone. The 5-HT1C antagonist with 5-HT2 agonist action, lisuride, also produced the HTR in a bell-shaped dose- and time-dependent fashion. Central injections of both (+/-)-DOI (0.2 mu g) and lisuride (0.5 mu g) also induced the behavior. Both peripheral and central administration of lisuride failed to produce the ESR. (+/-)-DOI significantly induced the ESR only at the highest dose tested (2.5 mg/kg, IF). Centrally administered (+/-)-DOI (0.2 mu g) produced more ESRs relative to vehicle controls; however, the difference did not attain significance. At low doses (0.31 and 0.63 mg/kg), (+/-)-DOI had no effect on locomotor activity, but it significantly attenuated the behavior at larger doses. Both low and high doses of lisuride increased the motor activity. Spiperone dose-dependently suppressed locomotion, whereas ketanserin had no effect. The present results suggest that the HTR is a 5-HT2 receptor-mediated event and changes in locomotor activity do not affect the induced HTR.