Young K A, Zavodny R, Hicks P B
Department of Medical Pharmacology and Toxicology, Texas A&M University College of Medicine, Olin E Teague Veterans Medical Center, Temple 76504.
Psychopharmacology (Berl). 1993;110(1-2):97-102. doi: 10.1007/BF02246956.
The interactions of serotonin 5-HT1A, 5-HT1C/2 and 5-HT3 receptor subtypes with apomorphine-induced locomotor activity (AILA) were investigated in Sprague-Dawley rats. The 5-HT3 antagonists ondansetron and ICS 205-930 had no significant effects on AILA. The 5-HT1A agonist 8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT) produced an increase in locomotor activity that was independent of DA neurotransmission. The locomotor activity induced by co-administration of apomorphine (APO; 0.25 mg/kg) and 8-OH-DPAT (0.25-1.0 mg/kg) was not significantly higher than those induced by APO alone during the peak period of APO stimulation of locomotor activity, nor were they higher than activity induced by 8-OH-DPAT alone during the same time intervals. The 5-HT1 antagonist (1)-propranolol had a depressant effect on AILA, but only at high doses. Coadministration of (1)-propranolol (5 mg/kg) and 8-OH-DPAT (1.0 mg/kg) elevated spontaneous locomotor activity for the first 10 min of the session when compared to 8-OH-DPAT (1.0 mg/kg) alone. The 5-HT2 antagonist ketanserin along with moderate and high doses of mesulergine depressed AILA, effects which may be mediated by the 5-HT2 antagonist properties of these drugs, by nonspecific sedation or by direct effects of these compounds on DA D2 receptors. In contrast to the high-dose mesulergine depression of AILA, a low dose (0.1 mg/kg) of mesulergine elevated AILA, an effect which was blocked by the 5-HT1C/2 agonist 1-(2,-5-dimethoxy-4-iodophenyl) -2-aminopropane (DOI; 1 mg/kg). Neither of these compounds at the doses tested had significant effects on spontaneous locomotor activity.(ABSTRACT TRUNCATED AT 250 WORDS)
在斯普拉格-道利大鼠中研究了血清素5-HT1A、5-HT1C/2和5-HT3受体亚型与阿扑吗啡诱导的运动活性（AILA）之间的相互作用。5-HT3拮抗剂昂丹司琼和ICS 205-930对AILA无显著影响。5-HT1A激动剂8-羟基-2-（二-N-丙基氨基）四氢萘（8-OH-DPAT）使运动活性增加，且该增加与多巴胺神经传递无关。在阿扑吗啡刺激运动活性的高峰期，联合给予阿扑吗啡（APO；0.25mg/kg）和8-OH-DPAT（0.25 - 1.0mg/kg）所诱导的运动活性并不显著高于单独给予APO所诱导的运动活性，在相同时间间隔内也不高于单独给予8-OH-DPAT所诱导的活性。5-HT1拮抗剂（1）-普萘洛尔对AILA有抑制作用，但仅在高剂量时。与单独给予8-OH-DPAT（1.0mg/kg）相比，联合给予（1）-普萘洛尔（5mg/kg）和8-OH-DPAT（1.0mg/kg）在实验的前10分钟提高了自发运动活性。5-HT2拮抗剂酮色林以及中高剂量的美舒麦角抑制AILA，这些作用可能是由这些药物的5-HT2拮抗剂特性、非特异性镇静作用或这些化合物对多巴胺D2受体的直接作用介导的。与高剂量美舒麦角抑制AILA相反，低剂量（0.1mg/kg）的美舒麦角提高了AILA，该作用可被5-HT1C/2激动剂1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI；1mg/kg）阻断。在所测试的剂量下，这两种化合物对自发运动活性均无显著影响。（摘要截断于250字）
