Campbell Joannalee C, Jeyamohan Shiveindra B, De La Cruz Priscilla, Chen Nita, Shin Damian, Pilitsis Julie G
Center for Neuropharmacology and Neuroscience, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA.
Department of Neurosurgery, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA.
Behav Brain Res. 2014 Dec 15;275:114-9. doi: 10.1016/j.bbr.2014.09.002. Epub 2014 Sep 6.
One potential complication of treating Parkinson's Disease (PD) with dopaminergic drugs is dopamine dysregulation syndrome, an addiction-like response to the drug therapy. Here, we assessed whether rats given parkinsonian-like symptoms with a unilateral injection of 6-hydroxydopamine into the medial forebrain bundle (6-OHDA-MFB), exhibit similar behavior. To examine this, we injected these rats or sham-lesioned rats subcutaneously (sc) with apomorphine (APO) at low (0.05mg/kg) and high (1mg/kg) dosage and monitored their conditioned place preference Saline was administered on alternating days. After 4 and 8 conditioned pairings, both rat groups underwent post-conditioning tests in a drug-free state 6-OHDA rats exhibited positive place conditioning to the low dose of APO after 4 and 8 pairings whereas sham-lesioned rats did not (p<0.01). At the high APO dose, sham-lesioned rats showed consistent positive place conditioning, but preferences in 6-OHDA rats were more variable although they all exhibited rotation behavior. Upon further inspection, we noted that contraversive rotation increased over time and this negatively correlated with place conditioning scores. While the absolute number of rotations did not negatively affect preference for the APO-paired chamber, an increase in rotation numbers between pairings did (r=-0.634, p=0.027). Taken together, 6-OHDA rats were more sensitive to the rewarding aspects of APO, but the adverse consequence of rotation diminished this response This model may be ideal to study addiction-like responses in PD.
用多巴胺能药物治疗帕金森病（PD）的一个潜在并发症是多巴胺调节障碍综合征，这是一种对药物治疗的成瘾样反应。在此，我们评估了通过向内侧前脑束单侧注射6-羟基多巴胺（6-OHDA-MFB）使大鼠出现帕金森样症状后，是否表现出类似行为。为了研究这一点，我们以低剂量（0.05mg/kg）和高剂量（1mg/kg）给这些大鼠或假手术大鼠皮下注射阿扑吗啡（APO），并监测它们的条件性位置偏爱。交替日给予生理盐水。在进行4次和8次条件配对后，两组大鼠均在无药物状态下接受条件后测试。6-OHDA大鼠在4次和8次配对后对低剂量APO表现出阳性位置条件反射，而假手术大鼠则没有（p<0.01）。在高剂量APO时，假手术大鼠表现出持续的阳性位置条件反射，但6-OHDA大鼠的偏爱更具变异性，尽管它们都表现出旋转行为。进一步检查时，我们注意到反向旋转随时间增加，且这与位置条件反射得分呈负相关。虽然旋转的绝对次数对APO配对室的偏爱没有负面影响，但配对之间旋转次数的增加却有影响（r=-0.634，p=0.027）。综上所述，6-OHDA大鼠对APO的奖赏方面更敏感，但旋转的不良后果减弱了这种反应。该模型可能是研究PD中成瘾样反应的理想模型。
