Melis M R, Succu S, Iannucci U, Argiolas A
Bernard B. Brodie Department of Neuroscience, University of Cagliari, Italy.
Eur J Pharmacol. 1997 Jun 11;328(2-3):115-23. doi: 10.1016/s0014-2999(97)83037-3.
A dose of N-methyl-D-aspartic acid (NMDA, 50 ng) that induces penile erection and yawning when injected into the paraventricular nucleus of the hypothalamus, increased the concentration of NO2- from 1.10 +/- 0.28 microM to 7.32 +/- 1.12 microM and of NO3 from 4.96 +/- 0.69 microM to 10.5 +/- 1.61 microM in the paraventricular dialysate obtained from male rats by in vivo microdialysis. NO2- concentration was not increased by (+/-)-alpha-(amino)-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA, 100 ng) or by trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD) (100 ng), which were unable to induce these behavioral responses. N-Methyl-D-aspartic acid effect on NO2- concentration, penile erection and yawning was prevented by dizolcipine (MK-801) (10-100 ng) or by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (20 microg), but not by the oxytocin receptor antagonist [d(CH2)5,Tyr(Me)2,Orn8]vasotocin (100 ng), or by the guanylate cyclase inhibitor methylene blue (20 microg) given in the paraventricular nucleus 15 min before N-methyl-D-aspartic acid or by the dopamine receptor antagonist haloperidol (0.5 mg/kg) given intraperitoneally 30 min before N-methyl-D-aspartic acid. In contrast, the nitric oxide scavenger hemoglobin (20 microg) given in the paraventricular nucleus prevented N-methyl-D-aspartic acid-induced NO2- concentration increase, but was unable to prevent penile erection and yawning. The results suggest that N-methyl-D-aspartic acid induces penile erection and yawning by increasing nitric oxide synthase activity in the paraventricular nucleus of the hypothalamus, possibly in the cell bodies of oxytocinergic neurons projecting to extra-hypothalamic brain areas and mediating these behavioral responses.
向下丘脑室旁核注射一剂N-甲基-D-天冬氨酸（NMDA，50纳克）可诱发阴茎勃起和打哈欠，通过体内微透析从雄性大鼠获得的室旁核透析液中，NO2-的浓度从1.10±0.28微摩尔/升增加到7.32±1.12微摩尔/升，NO3的浓度从4.96±0.69微摩尔/升增加到10.5±1.61微摩尔/升。（±）-α-（氨基）-3-羟基-5-甲基异恶唑-4-丙酸（AMPA，100纳克）或反式-（±）-1-氨基-1,3-环戊烷二羧酸（ACPD）（100纳克）不会增加NO2-浓度，它们也无法诱发这些行为反应。地卓西平（MK-801）（10 - 100纳克）或一氧化氮合酶抑制剂N（G）-硝基-L-精氨酸甲酯（20微克）可阻止N-甲基-D-天冬氨酸对NO2-浓度、阴茎勃起和打哈欠的影响，但在N-甲基-D-天冬氨酸注射前15分钟注入室旁核的催产素受体拮抗剂[d（CH2）5，Tyr（Me）2，Orn8]血管加压素（100纳克）、或鸟苷酸环化酶抑制剂亚甲蓝（20微克）、或在N-甲基-D-天冬氨酸注射前30分钟腹腔注射的多巴胺受体拮抗剂氟哌啶醇（0.5毫克/千克）则不能阻止。相反，在室旁核注入一氧化氮清除剂血红蛋白（20微克）可阻止N-甲基-D-天冬氨酸诱导的NO2-浓度增加，但无法阻止阴茎勃起和打哈欠。结果表明，N-甲基-D-天冬氨酸通过增加下丘脑室旁核中的一氧化氮合酶活性来诱发阴茎勃起和打哈欠，这可能发生在投射到下丘脑外脑区并介导这些行为反应的催产素能神经元的细胞体中。
