Engleman E A, Murphy J M, Zhou F C, Aprison M H, Hingtgen J N
Indiana University School of Medicine, Department of Psychiatry, Indianapolis, USA.
Pharmacol Biochem Behav. 1995 Nov;52(3):525-9. doi: 10.1016/0091-3057(95)00123-e.
Intracerebroventricular (ICV) administration of selective serotonergic agents was used to examine the extent of central mediation of 5-HTP-induced operant response suppression in rats. ICV administration of LY53857 (1.0, 3.75, or 7.5 micrograms/5 microliters/5 min) dose dependently blocked response suppression induced with systemically administered 5-HTP (25 mg/kg, IP), whereas ICV 0.9% saline (5 microliters over 5 min) had no significant effect on 5-HTP-induced response suppression. ICV ketanserin (7.5 micrograms/5 microliters/5 min) also blocked response suppression induced with systemically administered 5-HTP. ICV administration of the 5-HT2A/2C receptor agonist DOI (80 micrograms/5 microliters/5 min) induced significant periods of response suppression in this model, which was blocked with LY53857 (1.0 mg/kg, IP) pretreatment. These data demonstrate that central administration of 5-HT2A/2C antagonists potently attenuate operant response suppression induced with systemically administered 5-HTP or DOI and are in agreement with previous findings suggesting central mediation of 5-HTP-induced operant response suppression.
采用脑室内（ICV）注射选择性5-羟色胺能药物的方法，研究大鼠中5-羟色胺酸（5-HTP）诱导的操作性反应抑制的中枢介导程度。脑室内注射LY53857（1.0、3.75或7.5微克/5微升/5分钟）可剂量依赖性地阻断全身注射5-HTP（25毫克/千克，腹腔注射）诱导的反应抑制，而脑室内注射0.9%生理盐水（5分钟内注射5微升）对5-HTP诱导的反应抑制无显著影响。脑室内注射酮色林（7.5微克/5微升/5分钟）也可阻断全身注射5-HTP诱导的反应抑制。在该模型中，脑室内注射5-HT2A/2C受体激动剂DOI（80微克/5微升/5分钟）可诱导显著的反应抑制期，该抑制可被LY53857（1.0毫克/千克，腹腔注射）预处理阻断。这些数据表明，中枢给予5-HT2A/2C拮抗剂可有效减弱全身注射5-HTP或DOI诱导的操作性反应抑制，这与先前关于5-HTP诱导的操作性反应抑制存在中枢介导的研究结果一致。
