MCH and apomorphine in combination enhance action potential firing of nucleus accumbens shell neurons in vitro.
MCH and apomorphine in combination enhance action potential firing of nucleus accumbens shell neurons in vitro.
复制标题
作者：
Hopf FW;Seif T;Chung S;Civelli O
MCH和多巴胺受体系统已被证明可以调节与奖励处理、成瘾和神经精神疾病（如精神分裂症和抑郁症）相关的许多行为。此外，MCH和多巴胺受体可以积极地相互作用，例如在可卡因自我给药的表达中。最近的一份报告显示，DA1/DA2多巴胺受体激活剂阿波啡抑制脉冲前抑制，这是精神分裂症某些方面的临床前模型。重要的是，MCH可以增强低剂量阿波啡的作用，这表明多巴胺和MCH受体的共同调节可能减轻一些精神分裂症的症状，而多巴胺受体调节剂的剂量较低，从而减少潜在的副作用。在这里，我们研究了MCH和阿波啡是否可以增强伏隔核壳（NAshell）的动作电位放电，这一区域先前被证明介导了MCH的一些行为效应。利用全细胞膜片钳电生理学，我们发现MCH本身对放电没有影响，但当与亚阈值剂量的阿波啡联合使用时，能够增加纳什维尔放电。此外，DA1或DA2受体拮抗剂可以阻止MCH/apomorphine增加的放电，这表明apomorphine通过这两种受体类型来增强NAshell放电。MCH受体拮抗剂或PKA抑制剂也能阻止MCH/阿吗啡介导的放电增加。综上所述，我们的研究结果表明MCH可以与低剂量的阿波啡相互作用以增强纳什维尔放电，因此MCH和阿波啡可能在纳什维尔体内相互作用以抑制脉冲前抑制。
The MCH and dopamine receptor systems have been shown to modulate a number of behaviors related to reward processing, addiction, and neuropsychiatric conditions such as schizophrenia and depression. In addition, MCH and dopamine receptors can interact in a positive manner, for example in the expression of cocaine self-administration. A recent report showed that the DA1/DA2 dopamine receptor activator apomorphine suppresses pre-pulse inhibition, a preclinical model for some aspects of schizophrenia. Importantly, MCH can enhance the effects of lower doses of apomorphine, suggesting that co-modulation of dopamine and MCH receptors might alleviate some symptoms of schizophrenia with a lower dose of dopamine receptor modulator and thus fewer potential side effects. Here, we investigated whether MCH and apomorphine could enhance action potential firing in vitro in the nucleus accumbens shell (NAshell), a region which has previously been shown to mediate some behavioral effects of MCH. Using whole-cell patch-clamp electrophysiology, we found that MCH, which has no effect on firing on its own, was able to increase NAshell firing when combined with a subthreshold dose of apomorphine. Further, this MCH/apomorphine increase in firing was prevented by an antagonist of either a DA1 or a DA2 receptor, suggesting that apomorphine acts through both receptor types to enhance NAshell firing. The MCH/apomorphine-mediated firing increase was also prevented by an MCH receptor antagonist or a PKA inhibitor. Taken together, our results suggest that MCH can interact with lower doses of apomorphine to enhance NAshell firing, and thus that MCH and apomorphine might interact in vivo within the NAshell to suppress pre-pulse inhibition.
登录
查看更多内容
影响因子：
3.7
作者：
Devoto, Paola;Frau, Roberto;Bini, Valentina;Pillolla, Giuliano;Saba, Pierluigi;Flore, Giovanna;Corona, Marta;Marrosu, Francesco;Bortolato, Marco
通讯作者：
Bortolato, Marco
影响因子：
25
作者：
Goto, Y;Grace, AA
通讯作者：
Grace, AA
影响因子：
5.3
作者：
Hopf, FW;Mailliard, WS;Bonci, A
通讯作者：
Bonci, A
影响因子：
7.6
作者：
Besson, Morgane;Belin, David;Dalley, Jeffrey W.
通讯作者：
Dalley, Jeffrey W.
影响因子：
3.7
作者：
Chung S;Verheij MM;Hesseling P;van Vugt RW;Buell M;Belluzzi JD;Geyer MA;Martens GJ;Civelli O
通讯作者：
Civelli O