Department of Pharmacology, University of Michigan Medical School, 1301 MSRB III, 1150W. Medical Center Drive, Ann Arbor, MI 48109-0632, USA.
Psychopharmacology (Berl). 2011 Jun;215(4):609-20. doi: 10.1007/s00213-010-2154-7. Epub 2011 Jan 5.
Cocaine-induced changes in D(2) receptors have been implicated in the expression of sensitized behavioral responses and addiction-like behaviors; however, the influence of D(3) receptors is less clear.
To characterize the effects of repeated cocaine administration on the sensitivity of rats to D(2)- and D(3)-mediated behaviors, as well as the binding properties of ventral striatal D(2)-like and D(3) receptors.
Pramipexole was used to assess the sensitivity of rats to D(3)/D(2) agonist-induced yawning, hypothermia, and locomotor activity, 24 h, 72 h, 10, 21, and 42 days after repeated cocaine or saline administration. The locomotor effects of cocaine (42 day) and the binding properties of ventral striatal D(2)-like and D(3) receptors (24 h and 42 days) were also evaluated.
Cocaine-treated rats displayed an enhanced locomotor response to cocaine, as well as a progressive and persistent leftward/upward shift of the ascending limb (72 h-42 day) and leftward shift of the descending limb (42 days) of the pramipexole-induced yawning dose-response curve. Cocaine treatment also decreased B (max) and K (d) for D(2)-like receptors and increased D(3) receptor binding at 42 days. Cocaine treatment did not change pramipexole-induced hypothermia or locomotor activity or yawning induced by cholinergic or serotonergic agonists.
These studies suggest that temporal differences exist in the development of cocaine-induced sensitization of D(3) and D(2) receptors, with enhancements of D(3)-mediated behavioral effects observed within 72 h and enhancements of D(2)-mediated behavioral effects apparent 42 days after cocaine. These findings highlight the need to consider changes in D(3) receptor function when thinking about the behavioral plasticity that occurs during abstinence from cocaine use.
可卡因诱导的 D2 受体变化与敏化行为反应和类似成瘾的行为表达有关；然而，D3 受体的影响尚不清楚。
描述重复可卡因给药对大鼠 D2 和 D3 介导行为敏感性的影响，以及腹侧纹状体 D2 样和 D3 受体结合特性。
使用普拉克索评估大鼠对 D3/D2 激动剂诱导哈欠、体温过低和运动活动的敏感性，在重复可卡因或盐水给药后 24、72、10、21 和 42 天。还评估了可卡因（42 天）的运动作用和腹侧纹状体 D2 样和 D3 受体的结合特性（24 小时和 42 天）。
可卡因处理的大鼠对可卡因表现出增强的运动反应，以及普拉克索诱导的哈欠剂量反应曲线的上升支（72 小时至 42 天）和下降支（42 天）的渐进和持续的左移/上移。可卡因处理还降低了 D2 样受体的 Bmax 和 Kd，并增加了 42 天时 D3 受体结合。可卡因处理未改变普拉克索诱导的体温过低或运动活动，或胆碱能或 5-羟色胺能激动剂诱导的哈欠。
这些研究表明，在可卡因诱导的 D3 和 D2 受体敏化的发展中存在时间差异，在 72 小时内观察到 D3 介导的行为效应增强，而在可卡因后 42 天则明显增强 D2 介导的行为效应。这些发现强调了在考虑可卡因戒断期间发生的行为可塑性时，需要考虑 D3 受体功能的变化。
