LSD but not lisuride disrupts prepulse inhibition in rats by activating the 5-HT(2A) receptor.
LSD but not lisuride disrupts prepulse inhibition in rats by activating the 5-HT(2A) receptor.
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DOI：
10.1007/s00213-009-1718-x
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发表时间：
2010-02
影响因子：
3.4
通讯作者：
Geyer, Mark A.
中科院分区：
文献类型：
--
作者：
Halberstadt, Adam L.;Geyer, Mark A.
激活5-HT 2A受体的化合物，如麦角酸二乙胺（LSD），在人类中起致幻剂的作用。一个值得注意的例外是LSD同类物麦角脲，尽管它是一种有效的5-HT 2A激动剂，但对人类没有致幻作用。LSD和其他致幻剂已经被证明可以通过激活大鼠的5-HT 2A受体来破坏前脉冲抑制（PPI），这是一种感觉运动门控的操作措施。我们在雄性Sprague-Dawley大鼠中测试了麦角乙脲是否会破坏PPI。还进行了实验，以确定机制（S）负责的影响，麦角乙脲对PPI和比较的影响麦角乙脲的LSD。重复先前的报告，LSD（0.05、0.1和0.2 mg/kg，s.c.）降低PPI，LSD的作用被5-HT 2A选择性拮抗剂MDL 11，939预处理阻断。给药麦角脲（0.0375、0.075和0.15 mg/kg，s.c.）PPI也下降了。然而，用MDL 11，939或选择性5-HT 1A拮抗剂WAY-100635预处理不能阻断麦角脲（0.075 mg/kg）诱导的PPI破坏，但用选择性多巴胺D2/D3受体拮抗剂雷氯必利（0.1 mg/kg，s.c.）预处理可以预防。LSD对PPI的作用是由5-HT 2A受体介导的，而5-HT 2A受体的激活似乎并不有助于麦角乙脲对PPI的作用。这些发现表明，麦角乙脲和LSD通过不同的受体机制破坏PPI，并为麦角乙脲作为非致幻性5-HT 2A激动剂的分类提供了额外的支持。
Compounds that activate the 5-HT2A receptor, such as lysergic acid diethylamide (LSD), act as hallucinogens in humans. One notable exception is the LSD congener lisuride, which does not have hallucinogenic effects in humans even though it is a potent 5-HT2A agonist. LSD and other hallucinogens have been shown to disrupt prepulse inhibition (PPI), an operational measure of sensorimotor gating, by activating 5-HT2A receptors in rats. We tested whether lisuride disrupts PPI in male Sprague–Dawley rats. Experiments were also conducted to identify the mechanism(s) responsible for the effect of lisuride on PPI and to compare the effects of lisuride to those of LSD. Confirming a previous report, LSD (0.05, 0.1, and 0.2 mg/kg, s.c.) reduced PPI, and the effect of LSD was blocked by pretreatment with the selective 5-HT2A antagonist MDL 11,939. Administration of lisuride (0.0375, 0.075, and 0.15 mg/kg, s.c.) also reduced PPI. However, the PPI disruption induced by lisuride (0.075 mg/kg) was not blocked by pretreatment with MDL 11,939 or the selective 5-HT1A antagonist WAY-100635 but was prevented by pretreatment with the selective dopamine D2/D3 receptor antagonist raclopride (0.1 mg/kg, s.c). The effect of LSD on PPI is mediated by the 5-HT2A receptor, whereas activation of the 5-HT2A receptor does not appear to contribute to the effect of lisuride on PPI. These findings demonstrate that lisuride and LSD disrupt PPI via distinct receptor mechanisms and provide additional support for the classification of lisuride as a non-hallucinogenic 5-HT2A agonist.
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影响因子：
3.4
作者：
Halberstadt, Adam L.;Buell, Mahalah R.;Masten, Virginia L.;Risbrough, Victoria B.;Geyer, Mark A.
通讯作者：
Geyer, Mark A.
影响因子：
3.6
作者：
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通讯作者：
GERDES, GF
影响因子：
3.6
作者：
JOHANSSON, C;JACKSON, DM;SVENSSON, L
通讯作者：
SVENSSON, L
影响因子：
3.6
作者：
ADAMS, LM;GEYER, MA
通讯作者：
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影响因子：
4.7
作者：
Fitzgerald, LW;Conklin, DS;Hartig, PR
通讯作者：
Hartig, PR