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重复给予摇头丸会增加摇头丸引起的运动活动，并促进摇头丸自我给药的习得：多巴胺 D 受体机制的作用。

Repeated MDMA administration increases MDMA-produced locomotor activity and facilitates the acquisition of MDMA self-administration: role of dopamine D receptor mechanisms.

作者信息

van de Wetering Ross, Schenk Susan

机构信息

School of Psychology, Victoria University of Wellington, PO Box 600, Wellington, New Zealand.

出版信息

Psychopharmacology (Berl). 2017 Apr;234(7):1155-1164. doi: 10.1007/s00213-017-4554-4. Epub 2017 Feb 10.

DOI:10.1007/s00213-017-4554-4
PMID:28188355
Abstract

RATIONALE

Repeated exposure to ±3, 4-methylenedioxymethamphetamine (MDMA) produces sensitization to MDMA-produced hyperactivity, but the mechanisms underlying the development of this sensitized response or the relationship to the reinforcing effects of MDMA is unknown.

OBJECTIVES

This study determined the effect of a sensitizing regimen of MDMA exposure on the acquisition of MDMA self-administration and investigated the role of dopamine D receptor mechanisms.

METHODS

Rats received the selective D antagonist, eticlopride (0.0 or 0.3 mg/kg, i.p.) and MDMA (0.0 or 10.0 mg/kg, i.p.) during a five-day pretreatment regimen. Two days following the final session, the locomotor activating effects of MDMA (5 mg/kg, i.p.) and the latency to acquisition of MDMA self-administration were determined.

RESULTS

Pretreatment with MDMA enhanced the locomotor activating effects of MDMA and facilitated the acquisition of MDMA self-administration. Administration of eticlopride during MDMA pretreatment completely blocked the development of sensitization to MDMA-produced hyperactivity but failed to significantly alter the facilitated acquisition of MDMA self-administration. Pretreatment with eticlopride alone facilitated the acquisition of self-administration.

CONCLUSIONS

These data suggest that repeated MDMA exposure sensitized both the locomotor activating and reinforcing effects of MDMA. Activation of D receptors during MDMA pretreatment appears critical for the development of sensitization to MDMA-produced hyperactivity. The role of D receptor mechanisms in the development of sensitization to the reinforcing effects of MDMA is equivocal.

摘要

理论依据

反复接触±3,4-亚甲基二氧甲基苯丙胺（摇头丸）会导致对摇头丸引起的多动产生敏化作用，但这种敏化反应发展的潜在机制或与摇头丸强化作用的关系尚不清楚。

目的

本研究确定了摇头丸暴露的敏化方案对摇头丸自我给药习得的影响，并研究了多巴胺D受体机制的作用。

方法

在为期五天的预处理方案中，大鼠接受选择性D拮抗剂依托必利（0.0或0.3毫克/千克，腹腔注射）和摇头丸（0.0或10.0毫克/千克，腹腔注射）。在最后一次给药后的两天，测定摇头丸（5毫克/千克，腹腔注射）的运动激活作用和摇头丸自我给药的习得潜伏期。

结果

用摇头丸预处理可增强摇头丸的运动激活作用，并促进摇头丸自我给药的习得。在摇头丸预处理期间给予依托必利可完全阻断对摇头丸引起的多动的敏化发展，但未能显著改变摇头丸自我给药的促进习得。单独用依托必利预处理可促进自我给药的习得。

结论

这些数据表明，反复接触摇头丸会使摇头丸的运动激活和强化作用均产生敏化。在摇头丸预处理期间激活D受体似乎对摇头丸引起的多动的敏化发展至关重要。D受体机制在对摇头丸强化作用的敏化发展中的作用尚不清楚。

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