ADENOSINE A2A-RECEPTORS IN THE NUCLEUS-ACCUMBENS MEDIATE LOCOMOTOR DEPRESSION
ADENOSINE A2A-RECEPTORS IN THE NUCLEUS-ACCUMBENS MEDIATE LOCOMOTOR DEPRESSION
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DOI：
10.1016/0361-9230(93)90233-2
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发表时间：
1993-01-01
影响因子：
3.8
通讯作者：
NORMILE, HJ
中科院分区：
文献类型：
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作者：
BARRACO, RA;MARTENS, KA;NORMILE, HJ
在小鼠双侧伏核(ACB)注射后，观察了腺苷受体亚型选择性激动剂对运动活动(LA)的影响。ACB不仅由多巴胺(DA)能终末丰富地支配，而且在大脑中显示出最高密度的腺苷A2a受体。CGS 21680(2-[p-(2-carboxyethyl)phenethylamino]-5-N-ethylcarboxamidoadenosine)，是一种有效和高选择性的腺苷A2a受体激动剂，可引起LA明显的剂量相关减少(ID_(50)剂量=0.0031 nmol/小鼠)。混合腺苷受体激动剂NECA(5‘-N-乙基碳酰胺-腺苷)在纹状体A2a受体上显示出高的选择性和效力，类似地引起LA的剂量相关性减少(ID_(50)=0.0023 nmol/鼠)。相反，ACB内注射CPA(N6-环戊基腺苷)，一种高度选择性的腺苷A1受体激动剂，即使在2.0nmol/只小鼠体内也没有对LA产生任何显著影响，在这个剂量下，CGS 21680和NECA都将LA抑制了近90%，与载体对照组相比。此外，ACb内注射CGS 21680和NECA所引起的明显的运动抑制可被纹状体A2受体选择性拮抗剂DMPX(3，7-二甲基-1-炔丙基黄嘌呤)ip所显著拮抗，剂量为0.15mmo1/只对LA无明显影响。这些观察结果支持这样的观点，即腺苷可能通过密集聚集在腹侧纹状体的A2a受体的激动剂作用，选择性地调节DA介导的中脑边缘行为回路。
The effects on locomotor activity (LA) of selective agonists for adenosine receptor subtypes were examined in mice following bilateral injections into the nucleus accumbens (ACB). The ACB is not only richly innervated by dopaminergic (DA) terminals but also exhibits the highest densities of adenosine A2a receptors in the brain. CGS 21680 (2-[p-(2-carboxyethyl)phenethylamino]-5-N-ethylcarboxamidoadenosine), a potent and highly selective adenosine A2a receptor agonist, elicited pronounced, dose-related reductions in LA (ID50 dosage = 0.0031 nmol/mouse). NECA (5'-N-ethylcarboxamidoadenosine), a mixed adenosine receptor agonist which exhibits high selectivity and potency at striatal A2a receptors, similarly elicited dose-related reductions in LA (ID50 dosage = 0.0023 nmol/mouse). In contrast, intra-ACB injections of CPA (N6-cyclopentyladenosine), a highly selective agonist for adenosine A1 receptors, did not exert any significant effects on LA, even at 2.0 nmol/mouse, a dosage at which both CGS 21680 and NECA depressed LA by almost 90% compared to vehicle controls. Further, the pronounced locomotor depression elicited by intra-ACB injections of both CGS 21680 and NECA, at approximately the ID65 dosage, was significantly antagonized by IP pretreatment with DMPX, (3,7-dimethyl-1-propargylxanthine), an adenosine receptor antagonist with selectivity for A2 receptors in the striatum, at a dosage (0.15 mmol/mouse) which alone had no significant effect on LA. These observations provide support for the notion that adenosine may selectively modulate DA-mediated mesolimbic behavioral circuits via agonist actions at a population of A2a receptors densely concentrated in the ventral striatum.