McDougall Sanders A, Reichel Carmela M, Cyr Michelle C, Karper Patrick E, Nazarian Arbi, Crawford Cynthia A
Department of Psychology, California State University, San Bernardino, CA 92407, USA.
Psychopharmacology (Berl). 2005 Nov;183(1):20-30. doi: 10.1007/s00213-005-0146-9. Epub 2005 Oct 22.
Repeated exposure to psychostimulant drugs results in conditioned activity and behavioral sensitization. Nonassociative cellular changes are necessary for behavioral sensitization, while associative processes appear to modify the sensitized response.
The purpose of the present study was to determine whether the absence of the D(1) receptor would disrupt associative processes modulating sensitization and conditioned activity.
Wild-type and D(1) receptor knockout mice (i.e., D(1)-deficient mice) were injected with amphetamine (AMPH; 8 mg/kg, IP) before being placed in a previously novel test chamber (AMPH-Test group) or before being returned to the home cage (AMPH-Home group). Separate groups of mice were injected with saline (SAL) at the same time points. Distance traveled was measured 60 min each day, with the preexposure phase lasting 1 or 7 days. Sensitization was subsequently assessed after an injection of AMPH (1 mg/kg, IP), while conditioned activity was assessed after an injection of SAL.
After a 1-day preexposure phase, wild-type and D(1)-deficient mice exhibited similar patterns of sensitization and conditioned activity. After a 7-day preexposure phase, (1) D(1)-deficient mice exhibited more robust context-specific sensitization than wild-type mice, (2) only D(1)-deficient mice showed context-independent sensitization, and (3) only D(1)-deficient mice showed conditioned activity.
Repeatedly treating D(1)-deficient mice with AMPH appears to cause a general increase in responsivity. The reason for this hyper-responsivity is uncertain, but it is possible that cues from the testing environment were unable to inhibit responding (i.e., associative processes were disrupted). Alternatively, compensatory mechanisms (e.g., increases in D(2)-like receptors) may affect processes underlying sensitization and conditioned activity.
反复接触精神刺激药物会导致条件性活动和行为敏化。非联想性细胞变化是行为敏化所必需的，而联想过程似乎会改变敏化反应。
本研究的目的是确定缺乏D(1)受体是否会破坏调节敏化和条件性活动的联想过程。
野生型和D(1)受体基因敲除小鼠（即D(1)缺陷小鼠）在被放入先前陌生的测试箱（苯丙胺-测试组）之前或返回饲养笼之前（苯丙胺-家笼组）注射苯丙胺（AMPH；8mg/kg，腹腔注射）。在相同时间点给单独的小鼠组注射生理盐水（SAL）。每天测量60分钟的行进距离，预暴露阶段持续1天或7天。随后在注射AMPH（1mg/kg，腹腔注射）后评估敏化，在注射SAL后评估条件性活动。
在1天的预暴露阶段后，野生型和D(1)缺陷小鼠表现出相似的敏化和条件性活动模式。在7天的预暴露阶段后，（1）D(1)缺陷小鼠表现出比野生型小鼠更强的情境特异性敏化，（2）只有D(1)缺陷小鼠表现出与情境无关的敏化，（3）只有D(1)缺陷小鼠表现出条件性活动。
用AMPH反复处理D(1)缺陷小鼠似乎会导致反应性普遍增加。这种高反应性的原因尚不确定，但有可能测试环境中的线索无法抑制反应（即联想过程被破坏）。或者，补偿机制（例如，D(2)样受体增加）可能会影响敏化和条件性活动的潜在过程。
