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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Differences in the locomotor-activating effects of indirect serotonin agonists in habituated and non-habituated rats
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Differences in the locomotor-activating effects of indirect serotonin agonists in habituated and non-habituated rats

机译：习惯性和非习惯性大鼠间接5-羟色胺激动剂的运动激活作用差异

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The indirect serotonin (5-HT) agonist 3,4-methylenedioxymethamphetamine (MDMA) produces a distinct behavioral profile in rats consisting of locomotor hyperactivity, thigmotaxis, and decreased exploration. The indirect 5-HT agonist α-ethyltryptamine (AET) produces a similar behavioral profile. Using the Behavioral Pattern Monitor (BPM), the present investigation examined whether the effects of MDMA and AET are dependent on the novelty of the testing environment. These experiments were conducted in Sprague-Dawley rats housed on a reversed light cycle and tested during the dark phase of the light/dark cycle. We found that racemic MDMA (RS-MDMA; 3 mg/kg, SC) increased locomotor activity in rats tested in novel BPM chambers, but had no effect on locomotor activity in rats habituated to the BPM chambers immediately prior to testing. Likewise, AET (5 mg/kg, SC) increased locomotor activity in non-habituated animals but not in animals habituated to the test chambers. These results were unexpected because previous reports indicate that MDMA has robust locomotor-activating effects in habituated animals. To further examine the influence of habituation on MDMA-induced locomotor activity, we conducted parametric studies with S-(+)-MDMA (the more active enantiomer) in habituated and non-habituated rats housed on a standard or reversed light cycle. Light cycle was included as a variable due to reported differences in sensitivity to serotonergic ligands during the dark and light phases. In confirmation of our initial studies, rats tested during the dark phase and habituated to the BPM did not show an S-(+)-MDMA (3 mg/kg, SC)-induced increase in locomotor activity, whereas non-habituated rats did. By contrast, in rats tested during the light phase, S-(+)-MDMA increased locomotor activity in both non-habituated and habituated rats, although the response in habituated animals was attenuated. The finding that habituation and light cycle interact to influence MDMA- and AET-induced hyperactivity demonstrates that there are previously unrecognized complexities associated with the behavioral effects of these drugs.
机译：间接血清素（5-HT）激动剂3,4-亚甲二氧基甲基苯丙胺（MDMA）在大鼠中产生明显的行为特征，包括运动亢进，趋轴性和探索力下降。间接5-HT激动剂α-乙基色胺（AET）产生相似的行为特征。通过使用行为模式监视器（BPM），本研究检查了MDMA和AET的效果是否取决于测试环境的新颖性。这些实验是在以反向光照周期饲养的Sprague-Dawley大鼠中进行的，并在光照/黑暗周期的黑暗阶段进行了测试。我们发现外消旋的MDMA（RS-MDMA; 3 mg / kg，SC）增加了在新型BPM隔室中测试的大鼠的运动能力，但对刚适应BPM隔室的大鼠的运动能力没有影响。同样，AET（5 mg / kg，SC）在非习惯性动物中增加了运动能力，但在习惯于测试室的动物中却没有。这些结果是出乎意料的，因为以前的报道表明MDMA在习惯性动物中具有强大的运动激活作用。为了进一步研究习惯化对MDMA诱导的运动活性的影响，我们对以标准或反向光周期饲养的习惯和非习惯性大鼠中的S-（+）-MDMA（更具活性的对映异构体）进行了参数研究。由于报道了在黑暗和光明时期对血清素能配体的敏感性差异，因此将光循环作为变量包括在内。为了证实我们的初步研究，在黑暗期测试并习惯于BPM的大鼠未显示S-（+）-MDMA（3 mg / kg，SC）引起的运动能力增加，而非习惯性大鼠则表现出自发运动。相比之下，在光照阶段测试的大鼠中，S-（+）-MDMA可以提高非习惯性和习惯性大鼠的运动能力，尽管习惯性动物的反应减弱。习惯和轻循环相互作用影响MDMA和AET诱导的过度活跃的发现表明，以前存在与这些药物的行为效应相关的无法识别的复杂性。

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