Umathe S N, Wanjari M M, Manna S S S, Jain N S
Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Mahatma Jyotiba Fuley Shaikshanik Parisar, Amravati Road, Nagpur, Maharashtra 440 033, India.
Neuropeptides. 2009 Jun;43(3):251-7. doi: 10.1016/j.npep.2009.03.002. Epub 2009 Apr 28.
Haloperidol, an antipsychotic agent, stimulates the release of gonadotropin-releasing hormone (GnRH), and this hormone is known to mimic some of the behavioral effects of haloperidol. Hence, the present study was carried out to find out the contribution of GnRH in the behavioral effects of haloperidol. The studies revealed that haloperidol (0.15, 0.25 and 0.5 mg/kg, i.p.) and leuprolide (GnRH agonist; 50, 100, 200 and 400 microg/kg, s.c.) dose-dependently inhibited conditioned avoidance response (CAR) in male Sprague-Dawley rats. In higher doses, haloperidol (0.5, 1 mg/kg, i.p.) and leuprolide (200, 400 microg/kg, s.c.) produced catalepsy in rats. Co-administration of sub-effective dose of leuprolide (50 or 100 microg/kg, s.c.) and haloperidol (0.15 or 0.5 mg/kg, i.p.) similarly inhibited CAR and induced catalepsy. Pre-treatment of rats with antide (GnRH antagonist; 10 microg/rat, s.c.), attenuated the inhibitory effect of both the agents on CAR; blocked leuprolide-induced catalepsy; and attenuated the intensity and reduced the duration of haloperidol-induced catalepsy. In conclusion, the studies suggest a possible role of GnRH in the neuroleptic and cataleptic effect of haloperidol.
氟哌啶醇是一种抗精神病药物，它能刺激促性腺激素释放激素（GnRH）的释放，而这种激素已知能模拟氟哌啶醇的一些行为效应。因此，本研究旨在探究GnRH在氟哌啶醇行为效应中的作用。研究表明，氟哌啶醇（0.15、0.25和0.5mg/kg，腹腔注射）和亮丙瑞林（GnRH激动剂；50、100、200和400μg/kg，皮下注射）剂量依赖性地抑制雄性Sprague-Dawley大鼠的条件性回避反应（CAR）。在较高剂量下，氟哌啶醇（0.5、1mg/kg，腹腔注射）和亮丙瑞林（200、400μg/kg，皮下注射）可使大鼠产生僵住症。联合给予亚有效剂量的亮丙瑞林（50或100μg/kg，皮下注射）和氟哌啶醇（0.15或0.5mg/kg，腹腔注射）同样能抑制CAR并诱导僵住症。用安替肽（GnRH拮抗剂；10μg/只，皮下注射）对大鼠进行预处理，可减弱这两种药物对CAR的抑制作用；阻断亮丙瑞林诱导的僵住症；并减弱氟哌啶醇诱导的僵住症的强度和缩短其持续时间。总之，这些研究表明GnRH在氟哌啶醇的抗精神病和致僵住症效应中可能发挥作用。
