Florán Benjamín, Florán Leonor, Erlij David, Aceves Jorge
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Av. IPN 2508 San Pedro Zacatenco, Apartado Postal 14-740, 07360, México city, Mexico.
Neuropharmacology. 2004 Mar;46(4):497-503. doi: 10.1016/j.neuropharm.2003.10.004.
The thalamic reticular nucleus (nRt) is innervated by dopaminergic projections from the sustantia nigra compacta (SNc) and is rich in dopamine D4 receptors, however, the functional effects of dopamine on this structure are unknown. We examined whether the D1 receptor agonist SKF 38393, or the D2 class receptor agonist quinpirole, modify depolarization evoked Ca(2+)-dependent [3H]GABA release. SKF 38393 was without effects, whereas quinpirole inhibited [3H]GABA release with an IC50 of 81 +/- 33 nM. Dose-dependence determinations of agonists (quinpirole and PD 168, 077) and antagonists (L-745,870, U-101958, clozapine and raclopride) with different affinities for different D2 class subtype receptors showed that a D4 receptor mediates quinpirole inhibition. We used methylphenidate, an agent that acts by increasing interstitial dopamine, to determine whether endogenous dopamine modulates [3H]GABA release. Methylphenidate inhibited [3H]GABA release showing that the nRt contains sufficient endogenous dopamine to activate D4 receptors. This inhibition was completely reversed by selectively blocking D4 receptors with L-745,870 or U-101958 indicating that the catecholamine receptors that modulate GABA release are D4 receptors. Given the importance of the nRt in the control of attention, sensory processing and the generation of rhythmic activity during slow wave sleep, it is possible that abnormal nRt function may generate some of the manifestations of the disorders of dopaminergic transmission.
丘脑网状核（nRt）接受来自黑质致密部（SNc）的多巴胺能投射，且富含多巴胺D4受体，然而，多巴胺对该结构的功能影响尚不清楚。我们研究了D1受体激动剂SKF 38393或D2类受体激动剂喹吡罗是否会改变去极化诱发的Ca(2+)依赖性[3H]GABA释放。SKF 38393无作用，而喹吡罗抑制[3H]GABA释放，IC50为81±33 nM。对不同D2类亚型受体具有不同亲和力的激动剂（喹吡罗和PD 168,077）和拮抗剂（L-745,870、U-101958、氯氮平和雷氯必利）的剂量依赖性测定表明，D4受体介导喹吡罗的抑制作用。我们使用通过增加细胞间多巴胺起作用的哌甲酯来确定内源性多巴胺是否调节[3H]GABA释放。哌甲酯抑制[3H]GABA释放，表明nRt含有足够的内源性多巴胺来激活D4受体。用L-745,870或U-101958选择性阻断D4受体可完全逆转这种抑制作用，表明调节GABA释放的儿茶酚胺受体是D4受体。鉴于nRt在控制注意力、感觉处理以及慢波睡眠期间节律性活动产生中的重要性，nRt功能异常可能会产生多巴胺能传递障碍的一些表现。
