Wachtel S R, Hu X T, Galloway M P, White F J
Wayne State University School of Medicine, Department of Psychiatry, Detroit, Michigan.
Synapse. 1989;4(4):327-46. doi: 10.1002/syn.890040409.
Possible functional interactions between D1 and D2 dopamine (DA) receptors were examined using extracellular single-cell recording with microiontophoretic application of selective D1 and D2 receptor agonists both postsynaptically, in the rat nucleus accumbens (NAc) and caudate-putamen (CPu), and presynaptically, at impulse-regulating somatodendritic DA autoreceptors in the ventral tegmental area (A10) and substantia nigra pars compacta (A9). In addition, synthesis-modulating nerve terminal DA autoreceptors were studied in both the CPu and NAc using the gamma-butyrolactone (GBL) neurochemical model of isolated nerve terminal autoreceptor function in vivo. In both the NAc and CPu, the inhibition of neurons produced by iontophoresis of the D2 receptor agonists quinpirole or RU-24213 was attenuated by acute DA depletion via the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (AMPT). However, during iontophoresis of the selective D1 DA receptor agonist SKF 38393, the inhibitory effects of the D2 agonists were again evident, suggesting that the attenuation of D2 agonist-induced inhibition was due to decreased D1 receptor activation. In contrast, the inhibitory effects produced by the non-selective D1/D2 agonist apomorphine or by SKF 38393 were unaffected by AMPT pretreatment. Thus, D1 receptor activation appears necessary for D2 receptor-mediated inhibition of NAc and CPu neurons, whereas D2 receptor activation is not required for the inhibition produced by D1 receptor stimulation. In contrast to postsynaptic D2 receptors, the ability of DA agonists to stimulate D2 DA autoreceptors was not altered by manipulations of D1 receptor occupation. Enhancing D1 receptor stimulation with SKF 38393 or reducing D1 receptor occupation with either the selective D1 receptor antagonist SCH 23390 or AMPT failed to alter the rate-inhibitory effect of i.v. quinpirole on A9 or A10 DA neurons. Similarly, iontophoresis of SKF 38393 failed to alter the inhibitory effects of iontophoretic quinpirole. SKF 38393 also failed to affect the inhibition of GBL-induced increases in DOPA accumulation (tyrosine hydroxylase activity) produced by quinpirole in either the NAc or CPu. Furthermore, reversal of GBL-induced increases in DOPA accumulation by apomorphine or quinpirole was unaffected by pretreatment with SCH 23390. Therefore, D1 receptor occupation appears to be necessary for the expression of the functional effects of postsynaptic D2 receptor stimulation but not presynaptic D2 DA autoreceptor stimulation.
利用细胞外单细胞记录技术，通过微离子电泳法在大鼠伏隔核（NAc）和尾状核-壳核（CPu）的突触后以及腹侧被盖区（A10）和黑质致密部（A9）的冲动调节性树突状多巴胺自身受体的突触前，分别应用选择性D1和D2受体激动剂，研究了D1和D2多巴胺（DA）受体之间可能的功能相互作用。此外，使用γ-丁内酯（GBL）体内分离神经末梢自身受体功能的神经化学模型，在CPu和NAc中研究了合成调节性神经末梢DA自身受体。在NAc和CPu中，通过酪氨酸羟化酶抑制剂α-甲基-对-酪氨酸（AMPT）急性耗竭DA后，D2受体激动剂喹吡罗或RU-24213离子电泳产生的神经元抑制作用减弱。然而，在选择性D1 DA受体激动剂SKF 38393离子电泳期间，D2激动剂的抑制作用再次显现，表明D2激动剂诱导的抑制作用减弱是由于D1受体激活减少所致。相反，非选择性D1/D2激动剂阿扑吗啡或SKF 38393产生的抑制作用不受AMPT预处理的影响。因此，D1受体激活似乎是D2受体介导的对NAc和CPu神经元抑制所必需的，而D1受体刺激产生的抑制作用则不需要D2受体激活。与突触后D2受体相反，DA激动剂刺激D2 DA自身受体的能力不受D1受体占据操作的影响。用SKF 38393增强D1受体刺激或用选择性D1受体拮抗剂SCH 23390或AMPT减少D1受体占据均未能改变静脉注射喹吡罗对A9或A10 DA神经元的频率抑制作用。同样，SKF 38393离子电泳也未能改变喹吡罗离子电泳的抑制作用。SKF 38393也未能影响喹吡罗在NAc或CPu中对GBL诱导的多巴积累增加（酪氨酸羟化酶活性）的抑制作用。此外，阿扑吗啡或喹吡罗对GBL诱导的多巴积累增加的逆转不受SCH 23390预处理的影响。因此，D1受体占据似乎是突触后D2受体刺激功能效应表达所必需的，但不是突触前D2 DA自身受体刺激所必需的。
