Succu Salvatora, Sanna Fabrizio, Melis Tiziana, Boi Antonio, Argiolas Antonio, Melis Maria Rosaria
Bernard B Brodie Department of Neuroscience, Centre of Excellence for The Neurobiology of Addictions, University of Cagliari, S.P. Sestu-Monserrato, Km 0.700, 09042 Monserrato, CA, Italy.
Neuropharmacology. 2007 Mar;52(3):1034-43. doi: 10.1016/j.neuropharm.2006.10.019. Epub 2006 Dec 11.
The effect of a pro-erectile dose of apomorphine, a mixed dopamine receptor agonist, and of PD-168077 (N-[4-(2-cyanophenyl)piperazin-1-ylmethyl]-3-methylbenzamide maleate), a selective dopamine D4 receptor agonist, injected into the paraventricular nucleus of the hypothalamus on the concentration of extra-cellular dopamine and its main metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the dialysate from the nucleus accumbens was studied in male rats. As expected, apomorphine (0.1microg) and PD-168077 (0.1microg) induced penile erection episodes, which occurred concomitantly to an increase in extra-cellular dopamine and DOPAC concentration in the dialysate from the shell of the nucleus accumbens, as measured by intracerebral microdialysis. When induced by apomorphine, these effects were reduced by 80% by raclopride, a selective D2/D3 receptor antagonist (1microg) and only by 40-45% by L-745,870 (1microg), a selective dopamine D4 receptor antagonist. When induced by PD-168077, these effects were reduced by more than 80% by L-745,870 (1microg), but only by 35-40% by raclopride. Irrespective of the dopamine agonist used to induce penile erection, the pro-erectile effect and the concomitant increase in dopamine and DOPAC concentration in the nucleus accumbens dialysate were almost completely abolished by d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin(1microg), a potent oxytocin receptor antagonist, given into the lateral ventricles. The present results suggest that stimulation of dopamine receptors (mainly of the D2 to D4 subtype) in the paraventricular nucleus induces the release of oxytocin in brain areas that influence the activity of mesolimbic dopaminergic neurons mediating the appetitive and reinforcing effects of sexual activity. This provides evidence for a role of oxytocin in neural circuits that integrate the activity of neural pathways controlling the consummatory aspects of sexual behaviour (e.g., penile erection) with those controlling sexual motivation and sexual arousal.
在雄性大鼠中，研究了将促勃起剂量的阿扑吗啡（一种混合多巴胺受体激动剂）和PD - 168077（马来酸N - [4 - (2 - 氰基苯基)哌嗪 - 1 - 基甲基]-3 - 甲基苯甲酰胺）（一种选择性多巴胺D4受体激动剂）注射到下丘脑室旁核后，对伏隔核透析液中细胞外多巴胺及其主要代谢物3,4 - 二羟基苯乙酸（DOPAC）浓度的影响。如预期的那样，阿扑吗啡（0.1微克）和PD - 168077（0.1微克）诱导阴茎勃起发作，同时通过脑内微透析测量发现，伏隔核壳部透析液中的细胞外多巴胺和DOPAC浓度增加。当由阿扑吗啡诱导时，这些效应被选择性D2/D3受体拮抗剂雷氯必利（1微克）降低了80%，而被选择性多巴胺D4受体拮抗剂L - 745,870（1微克）仅降低了40 - 45%。当由PD - 168077诱导时，这些效应被L - 745,870（1微克）降低了80%以上，但被雷氯必利仅降低了35 - 40%。无论使用哪种多巴胺激动剂诱导阴茎勃起，将强效催产素受体拮抗剂d(CH(2))(5)Tyr(Me)(2)-Orn(8)-血管加压素（1微克）注入侧脑室后，促勃起效应以及伏隔核透析液中多巴胺和DOPAC浓度的相应增加几乎完全被消除。目前的结果表明，刺激室旁核中的多巴胺受体（主要是D2至D4亚型）会诱导催产素在影响中脑边缘多巴胺能神经元活动的脑区释放，这些神经元介导性活动的食欲和强化作用。这为催产素在神经回路中的作用提供了证据，该神经回路整合了控制性行为（如阴茎勃起）的完成方面的神经通路活动与控制性动机和性唤起的神经通路活动。
