Antipsychotic-like profile of combined treatment with raclopride and 8-OH-DPAT in the rat: enhancement of antipsychotic-like effects without catalepsy
Antipsychotic-like profile of combined treatment with raclopride and 8-OH-DPAT in the rat: enhancement of antipsychotic-like effects without catalepsy
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DOI：
10.1007/bf01244451
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
M. Wadenberg;S. Ahlénius
中科院分区：
文献类型：
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作者：
M. Wadenberg;S. Ahlénius
给予5-HT 1A激动剂8-OH-DPAT，0.1 mg kg− 1 sc −20 min，对大鼠的条件回避行为产生中度抑制（对照组的60%）。然而，在较高剂量（0.4和1.6 mg kg− 1 sc）给药后未观察到该效应。试验间杂交的数量不受较低剂量的影响，但通过施用两个较高剂量的8-OH-DPAT而显著增加。多巴胺D2受体阻断剂雷氯必利（0.05 mg kg−1）本身不能抑制回避行为，但与8-OH-DPAT联合使用时，回避行为（对照组的30%）以及试验间杂交均受到抑制。雷氯必利（0.1 mg kg− 1 sc）或8-OH-DPAT（0.1 mg kg− 1 sc）可抑制旷场自发活动。联合给药进一步抑制了自发活动，并显著增加了“不动性”（静止运动）。跑步机运动，但是，不受任何化合物本身，而联合治疗损害跑步机性能。较高剂量雷氯必利（0.4 mg kg− 1 sc）对跑台运动能力的抑制作用，并未因额外给予8-OH-DPAT（0.1 mg kg−1）而改变。与8-OH-DPAT和雷氯必利对条件性回避行为、旷场运动和跑台运动表现的累加效应相反，雷氯必利（16 mg kg− 1）产生的僵住症可被8-OH-DPAT（0.1 mg kg−1）完全拮抗。总之，目前的研究结果表明，5-HT激动剂和DA D2拮抗剂在大鼠抗精神病样作用和锥体外系运动效应的一些关键试验中具有很强的相互作用，并为寻找具有更高临床疗效和更少锥体外系副作用的新型抗精神病药物提供了新的可能性
The administration of the 5-HT1Aagonist 8-OH-DPAT, 0.1 mg kg−1sc −20 min, produced a moderate suppression of conditioned avoidance behavior (60% of controls) in the rat. This effect, however, was not seen after administration of higher doses, 0.4 and 1.6 mg kg−1sc. The number of intertriai crosses were not affected by the lower dose but significantly increased by administration of the two higher doses of 8-OH-DPAT. The dopamine D2receptor blocking agent raclopride, 0.05 mg kg−1, by itself did not suppress the avoidance behavior, but in combination with 8-OH-DPAT produced suppression of avoidance behavior (30% of controls) as well as intertrial crosses. Open field locomotor activity was suppressed by raclopride, 0.1 mg kg−1sc, or by 8-OH-DPAT, 0.1 mg kg−1sc. The combined treatment produced a further suppression of locomotor activity and a marked increase in “immobility” (stationary movements). Treadmill locomotion, however, was not affected by either compound by itself, whereas the combined treatment impaired treadmill performance. Suppression of treadmill performance by a higher dose of raclopride, 0.4 mg kg−1sc, was not altered by the additional treatment with 8-OH-DPAT, 0.1 mg kg−1. In contrast to the additive effects of 8-OH-DPAT and raclopride on conditioned avoidance behavior, open field locomotion and treadmill performance, the catalepsy produced by raclopride, 16 mg kg−1was completely antagonised by treatment with 8-OH-DPAT 0.1 mg kg−1. Taken together, the present findings demonstrate strong interactions between a 5-HT agonist and a DA D2antagonist on some critical tests for antipsychotic-like actions and extrapyramidal motor effects in rats, and suggest new possibilities in the search for new antipsychotic drugs with higher clinical efficacy and less extrapyramidal side effects