Romeas Thomas, Morissette Marie-Claude, Mnie-Filali Ouissame, Piñeyro Graciela, Boye Sandra M
Department of Pharmacology, University of Montreal, Montreal, Quebec, Canada.
Psychopharmacology (Berl). 2009 Aug;205(2):293-303. doi: 10.1007/s00213-009-1539-y. Epub 2009 Apr 29.
Anhedonia, or hyposensitivity to normally pleasurable stimuli, is a cardinal symptom of depression. As such, reward circuitry may comprise a substrate with relevance to this symptom of depression.
Our aim was to characterize in the rat changes in the rewarding properties of a pharmacological and a natural stimulus following olfactory bulbectomy (OBX), a pre-clinical animal model of depression.
We measured amphetamine enhancement of brain stimulation reward, changes in sucrose intake, as well as striatal cAMP response element binding protein (CREB) activity, a molecular index previously associated with depressant-like behavior. Moreover, since alteration of psychomotor activity is also a common symptom of depression, and psychostimulant reward and locomotion are thought to share common neurobiology, we used the same treatment schedule of amphetamine to probe for changes in locomotion.
Our findings show that OBX produces a behavioral phenotype characterized by both anhedonia and exaggerated locomotor activation. Thus, we observed a blunted response to the rewarding properties of amphetamine (1 mg/kg, 21 days post-lesion), a long-lasting reduction in sucrose intake and increased striatal CREB activity. In addition, the same dose of amphetamine, at a coincident time post-lesion, triggered an exaggerated response to its locomotor-stimulant actions.
These paradoxical findings are not consistent with the notion that reward and locomotion are mediated by a common substrate; this dissociation may be useful in modeling psychiatric disorders such as mixed depressive states. In addition, our findings suggest that central reward circuitry may constitute a possible target for rationally designed therapeutics for depression.
快感缺失，即对通常令人愉悦的刺激反应迟钝，是抑郁症的主要症状。因此，奖赏回路可能是与抑郁症这一症状相关的基础。
我们的目的是在嗅球切除（OBX）后的大鼠中，描述一种药理学刺激和一种自然刺激的奖赏特性变化，OBX是一种抑郁症临床前动物模型。
我们测量了苯丙胺对脑刺激奖赏的增强作用、蔗糖摄入量的变化以及纹状体环磷腺苷反应元件结合蛋白（CREB）的活性，CREB活性是一种先前与抑郁样行为相关的分子指标。此外，由于精神运动活动的改变也是抑郁症的常见症状，并且精神兴奋剂奖赏和运动被认为共享共同的神经生物学机制，我们使用相同的苯丙胺治疗方案来探究运动的变化。
我们的研究结果表明，OBX产生了一种以快感缺失和过度运动激活为特征的行为表型。因此，我们观察到对苯丙胺奖赏特性的反应减弱（1mg/kg，损伤后21天）、蔗糖摄入量长期减少以及纹状体CREB活性增加。此外，相同剂量的苯丙胺在损伤后的同一时间引发了对其运动刺激作用的过度反应。
这些矛盾的发现与奖赏和运动由共同基础介导的观点不一致；这种分离可能有助于模拟诸如混合抑郁状态等精神疾病。此外，我们的研究结果表明，中枢奖赏回路可能构成抑郁症合理设计治疗方法的一个可能靶点。
