Anagnostakis Y, Kastellakis A, Spyraki C
Department of Basic Sciences, School of Medicine, University of Crete, Heraklion, Greece.
Eur Neuropsychopharmacol. 1998 Feb;8(1):47-53. doi: 10.1016/s0924-977x(97)00044-8.
It has been hypothesized that the intrapallidal morphine-induced dopamine release in the nucleus accumbens may be mediated by thalamocorticostriatal or mesolimbic pathways. In order to challenge the above hypothesis, we examined whether changes in accumbal dopamine and its metabolites produced by intrapallidal morphine a) are associated with local excitatory amino acid neurotransmission b) are determined by impulse propagation in dopamine neurons and c) are observed both ipsi- and contralateral to the morphine administration site. In vivo microdialysis was used to assess dopamine release and metabolism in the right and the left nucleus accumbens separately of awake, unrestrained rats. Vehicle or morphine hydrochloride (10 microliters/26.0 mM) was applied unilaterally into the pallidum alone or in combination with ipsilateral application of the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) into the nucleus accumbens or the sodium channel blocker tetrodotoxin into the medial forebrain bundle. Drugs' application was performed via reverse dialysis. Concentrations of dopamine, 3,4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) in the collected dialysate were measured by high performance liquid chromatography with electrochemical detection. Morphine administration resulted in elevated levels of dopamine in the ipsilateral and of DOPAC and HVA in both the ipsi- and contralateral nucleus accumbens. Dizocilpine (MK-801) (0.3 mM) did not influence the basal levels of dopamine, DOPAC or HVA in the nucleus accumbens. Ipsilaterally, dizocilpine (MK-801) inhibited the effect of morphine on dopamine release, whereas it increased significantly the effect of the drug on DOPAC and HVA. Tetrodotoxin (3 microM) reversed the effect of intrapallidal morphine on dopamine, DOPAC or HVA in the ipsilateral nucleus accumbens. The results show that the intrapallidal morphine-induced dopaminergic activation in the ipsilateral nucleus accumbens is dependent upon both phasic and tonic activation of dopaminergic neurons. They suggest that both the thalamocorticostriatal and the mesolimbic dopamine pathways may mediate the investigated effect of morphine.
据推测，苍白球内注射吗啡引起的伏隔核多巴胺释放可能由丘脑皮质纹状体或中脑边缘通路介导。为了验证上述假设，我们研究了苍白球内注射吗啡所引起的伏隔核多巴胺及其代谢产物的变化是否：a）与局部兴奋性氨基酸神经传递有关；b）由多巴胺能神经元的冲动传导所决定；c）在吗啡给药部位的同侧和对侧均能观察到。采用体内微透析技术，分别评估清醒、自由活动大鼠左右伏隔核中的多巴胺释放及代谢情况。将溶媒或盐酸吗啡（10微升/26.0毫摩尔）单侧注入苍白球，或同时向伏隔核同侧注入N-甲基-D-天冬氨酸（NMDA）受体拮抗剂地佐环平（MK-801），或向内侧前脑束注入钠通道阻滞剂河豚毒素。通过反向透析给药。采用高效液相色谱-电化学检测法测定收集到的透析液中多巴胺、3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）的浓度。注射吗啡后，同侧伏隔核多巴胺水平升高，同侧和对侧伏隔核的DOPAC和HVA水平均升高。地佐环平（MK-801）（0.3毫摩尔）不影响伏隔核中多巴胺、DOPAC或HVA的基础水平。在同侧，地佐环平（MK-801）抑制吗啡对多巴胺释放的作用，而显著增强药物对DOPAC和HVA的作用。河豚毒素（3微摩尔）可逆转苍白球内注射吗啡对同侧伏隔核多巴胺、DOPAC或HVA的作用。结果表明，苍白球内注射吗啡引起的同侧伏隔核多巴胺能激活依赖于多巴胺能神经元的相位性和紧张性激活。提示丘脑皮质纹状体和中脑边缘多巴胺通路可能均介导了吗啡的上述作用。
