Di Matteo V, Di Giovanni G, Di Mascio M, Esposito E
Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Chieti, Italy.
Neuropharmacology. 1998;37(2):265-72. doi: 10.1016/s0028-3908(98)00014-8.
The effects of mesulergine (100 and 200 microg/kg s.c.), SB 206553 (1 and 2.5 mg/kg i.p.), RP 62203 (2.5 and 4 mg/kg i.p.) and ritanserin (630 microg/kg i.p.) were studied on the extracellular concentration of dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens of chloral hydrate-anesthetized rats, using intracerebral microdialysis. Mesulergine, a non selective serotonin2C/2B/2A (5-HT2C/2B/2A) receptor antagonist, significantly increased DA release, which reached a peak level (+ 20%) 60 min after drug injection and slowly returned back to baseline values. Mesulergine also caused a dose-dependent increase in DOPAC outflow. Pretreatment with mesulergine (200 microg/kg) did not change the inhibition of DA release induced by apomorphine (100 microg/kg), whereas it prevented the reduction of DOPAC outflow induced by apomorphine (100 microg/kg). Administration of SB 206553, a selective blocker of 5-HT2C/2B receptors, dose-dependently increased DA outflow. The dose of 2.5 mg/kg SB 206553 caused a linear increase of DA output which reached a peak (+75%) 40 min after injection, while 1 mg/kg induced a more gradual increase of DA release which peaked (+54%) 60 min after administration of the drug. Treatment with RP 62203, a selective 5-HT2A receptor antagonist, did not produce any significant effect on DA outflow. Administration of ritanserin, a mixed 5-HT2A/2C receptor antagonist, did not cause any significant change of DA and DOPAC outflow. Taken together, these data indicate that selective blockade of 5-HT2/2B receptor subtypes increases DA release in the rat nucleus accumbens.
采用脑内微透析技术，研究了美舒麦角（100和200微克/千克，皮下注射）、SB 206553（1和2.5毫克/千克，腹腔注射）、RP 62203（2.5和4毫克/千克，腹腔注射）和利坦色林（630微克/千克，腹腔注射）对水合氯醛麻醉大鼠伏隔核细胞外多巴胺（DA）和二羟基苯乙酸（DOPAC）浓度的影响。美舒麦角是一种非选择性5-羟色胺2C/2B/2A（5-HT2C/2B/2A）受体拮抗剂，可显著增加DA释放，在注射药物后60分钟达到峰值水平（增加20%），然后缓慢恢复到基线值。美舒麦角还导致DOPAC流出量呈剂量依赖性增加。预先给予美舒麦角（200微克/千克）不会改变阿扑吗啡（100微克/千克）诱导的DA释放抑制作用，但可防止阿扑吗啡（100微克/千克）诱导的DOPAC流出量减少。给予选择性5-HT2C/2B受体阻滞剂SB 206553可使DA流出量呈剂量依赖性增加。2.5毫克/千克的SB 206553剂量可使DA输出呈线性增加，在注射后40分钟达到峰值（增加75%），而1毫克/千克则使DA释放增加更为缓慢，在给药后60分钟达到峰值（增加54%）。给予选择性5-HT2A受体拮抗剂RP 62203对DA流出量没有产生任何显著影响。给予混合性5-HT2A/2C受体拮抗剂利坦色林不会导致DA和DOPAC流出量发生任何显著变化。综上所述，这些数据表明选择性阻断5-HT2/2B受体亚型可增加大鼠伏隔核中的DA释放。
