Neuropathy is major source of chronic pain that can be caused by mechanically or chemically induced nerve injury. Intraplantar formalin injection produces local necrosis over a two-week period and has been used to model neuropathy in rats. To determine whether neuropathy alters dopamine (DA) receptor responsiveness in mesolimbic brain regions, we examined dopamine D1-like and D2-like receptor (D1/2R) signaling and expression in male rats 14 days after bilateral intraplantar formalin injections into both rear paws. D2R-mediated G-protein activation and expression of the D2R long, but not short, isoform were reduced in nucleus accumbens (NAc) core, but not in NAc shell, caudate-putamen or ventral tegmental area of formalin- compared to saline-treated rats. In addition, D1R-stimulated adenylyl cyclase activity was also reduced in NAc core, but not in NAc shell or prefrontal cortex, of formalin-treated rats, whereas D1R expression was unaffected. Other proteins involved in dopamine neurotransmission, including dopamine uptake transporter and tyrosine hydroxylase, were unaffected by formalin treatment. In behavioral tests, the potency of a D2R agonist to suppress intracranial self-stimulation (ICSS) was decreased in formalin-treated rats, whereas D1R agonist effects were not altered. The combination of reduced D2R expression and signaling in NAc core with reduced suppression of ICSS responding by a D2R agonist suggest a reduction in D2 autoreceptor function. Altogether, these results indicate that intraplantar formalin produces attenuation of highly specific DA receptor signaling processes in NAc core of male rats and suggest the development of a neuropathy-induced allostatic state in both pre- and post-synaptic DA receptor function.

中文翻译：

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在化学诱导的神经病大鼠模型中伏伏核核心中的多巴胺受体信号减弱。

神经病是机械或化学诱导的神经损伤可能引起的慢性疼痛的主要来源。足底福尔马林注射在两周内产生局部坏死，已被用于模拟大鼠的神经病变。为了确定神经病是否会改变中脑边缘大脑区域的多巴胺（DA）受体反应性，我们在双侧足底福尔马林注射至两只后爪后14天，检查了雄性大鼠的多巴胺D1样和D2样受体（D1 / 2R）信号传导和表达。与生理盐水处理组相比，伏隔蛋白核（NAc）核心中D2R介导的G蛋白激活和D2R长但不短的同工型表达减少，但NAc壳，尾状豆腐或腹侧被盖区域中D2R的同种型减少，但不减少大鼠。此外，NAc核心中D1R刺激的腺苷酸环化酶活性也降低了，但福尔马林处理过的大鼠的NAc外壳或前额叶皮层中没有，而D1R表达不受影响。参与多巴胺神经传递的其他蛋白质，包括多巴胺摄取转运蛋白和酪氨酸羟化酶，均未受到福尔马林治疗的影响。在行为测试中，福尔马林治疗的大鼠中D2R激动剂抑制颅内自我刺激（ICSS）的能力降低，而D1R激动剂的作用没有改变。减少的D2R表达和NAc核心中的信号传递与减少的DCSS激动剂对ICSS的抑制相结合，表明D2自体受体功能的下降。共，