Mitrovic Igor, Napier T Celeste
Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago Stritch School of Medicine, Building 102, 2160 South First Avenue, Maywood, IL 60153, USA.
Eur J Neurosci. 2002 Jan;15(2):257-68. doi: 10.1046/j.0953-816x.2001.01860.x.
The ventral pallidum (VP) is situated at the convergence of midbrain dopamine and accumbal opioid efferent projections. Using in vivo electrophysiological procedures in chloral hydrate-anaesthetized rats, we examined whether discrete application of mu- [D-Ala2,N-Me-Phe4,Gly-ol5 (DAMGO)] or kappa- (U50488) opioid receptor agonists could alter VP responses to electrical stimulation of ventral tegmental area. Rate suppressions occurred frequently following ventral tegmental area stimulation. Consistent with an involvement of dopamine in this effect, none of the 12 spontaneously active ventral pallidal neurons recorded in rats that had monoamines depleted by reserpine responded to electrical stimulation of ventral tegmental area. Moreover, in intact rats, the dopamine antagonist flupenthixol attenuated evoked suppression in 100% of the neurons tested; however, the GABAA antagonist bicuculline was able to slightly attenuate the response in 50% of the neurons tested. These observations concur with our previous studies in indicating that ventral tegmental area stimulation releases dopamine (and sometimes GABA) onto ventral pallidal neurons. Both DAMGO and U50488 decreased the inhibitory effects of ventral tegmental area stimulation. These effects on the endogenously released transmitter differed from those seen with exogenously applied dopamine, for DAMGO did not alter the efficacy or potency of microiontophoretically applied dopamine. Taken together, these observations suggest that the interaction between DAMGO and dopamine does not occur at a site that is immediately postsynaptic to the dopaminergic input within the VP, but rather that opioid modulation involves mechanisms governing presynaptically released dopamine. These modulatory processes would enable ventral pallidal opioids to gate the influence of ventral tegmental area dopamine transmission on limbic system outputs at the level of the VP.
腹侧苍白球（VP）位于中脑多巴胺能和伏隔核阿片传出投射的交汇点。我们采用水合氯醛麻醉大鼠的体内电生理方法，研究了μ- [D-丙氨酸2，N-甲基苯丙氨酸4，甘醇5（DAMGO）]或κ-（U50488）阿片受体激动剂的离散应用是否能改变VP对腹侧被盖区电刺激的反应。腹侧被盖区刺激后经常出现频率抑制。与多巴胺参与此效应一致，在通过利血平使单胺耗竭的大鼠中记录的12个自发活动的腹侧苍白球神经元中，没有一个对腹侧被盖区的电刺激有反应。此外，在完整大鼠中，多巴胺拮抗剂氟奋乃静在100%的测试神经元中减弱了诱发的抑制；然而，GABAA拮抗剂荷包牡丹碱能够在50%的测试神经元中轻微减弱反应。这些观察结果与我们之前的研究一致，表明腹侧被盖区刺激将多巴胺（有时还有GABA）释放到腹侧苍白球神经元上。DAMGO和U50488都降低了腹侧被盖区刺激的抑制作用。这些对内源性释放递质的作用与外源性应用多巴胺所见不同，因为DAMGO没有改变微量离子电泳应用多巴胺的效力或效能。综上所述，这些观察结果表明，DAMGO与多巴胺之间的相互作用并非发生在VP内多巴胺能输入的紧邻突触后位点，而是阿片类调制涉及控制突触前释放多巴胺的机制。这些调制过程将使腹侧苍白球阿片类物质在VP水平上调节腹侧被盖区多巴胺传递对边缘系统输出的影响。
