Umathe Sudhir, Bhutada Pravinkumar, Dixit Pankaj, Shende Varsha
Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440033, Maharashtra, India.
Eur J Pharmacol. 2008 Jun 10;587(1-3):175-80. doi: 10.1016/j.ejphar.2008.03.035. Epub 2008 Apr 1.
A characteristic behavior in alcohol abstinence state indicates the possibility of obsessive-compulsive behavior in alcoholics. Ethanol is known to reduce hypothalamic synthesis, release, and mRNA expression of gonadotropin-releasing hormone (GnRH) that modulates serotonergic, dopaminergic, and glutamatergic systems, which experience adaptive changes on chronic exposure to ethanol. Such changes are also evident in obsessive-compulsive disorder. Therefore, it was proposed to investigate the effect of ethanol-withdrawal on marble-burying behavior in mice, particularly because it simulates some aspects of obsessive-compulsive behavior; further, the influence of GnRH agonist was studied on the same. Ethanol-withdrawal state was induced after its chronic administration, and marble-burying behavior was observed at 0, 6, 24, 48, and 96 h interval. Further, the influence of leuprolide--a GnRH agonist (50-600 microg/kg, s.c.) or fluoxetine (5-30 mg/kg, i.p.) was investigated on ethanol-withdrawal-induced changes in marble-burying behavior. The results indicated that ethanol-withdrawal led to a gradual increase in marble-burying behavior upto 48 h with peak at 24 h interval. Administration of leuprolide (100-600 microg/kg, s.c.), 30 min prior to 24 h interval, dose dependently reduced ethanol-withdrawal-induced increase in marble-burying behavior, and this effect was comparable to that of fluoxetine (15 and 30 mg/kg, i.p.). Further, twice daily administration of leuprolide (50 microg/kg, s.c), concomitant with ethanol, prevented the gradual increase in marble-burying behavior after ethanol-withdrawal and this effect was comparable to fluoxetine (5 mg/kg, i.p.). In conclusion, ethanol-withdrawal on chronic administration increases marble-burying behavior in mice; its development and expression is attenuated by leuprolide.
酒精戒断状态下的一种特征性行为表明酗酒者存在强迫行为的可能性。已知乙醇会降低促性腺激素释放激素（GnRH）的下丘脑合成、释放及mRNA表达，而GnRH可调节血清素能、多巴胺能和谷氨酸能系统，这些系统在长期接触乙醇后会发生适应性变化。这种变化在强迫症中也很明显。因此，有人提出研究乙醇戒断对小鼠埋大理石行为的影响，特别是因为它模拟了强迫行为的某些方面；此外，还研究了GnRH激动剂对其的影响。在长期给予乙醇后诱导出乙醇戒断状态，并在0、6、24、48和96小时间隔观察埋大理石行为。此外，研究了亮丙瑞林（一种GnRH激动剂，50 - 600微克/千克，皮下注射）或氟西汀（5 - 30毫克/千克，腹腔注射）对乙醇戒断诱导的埋大理石行为变化的影响。结果表明，乙醇戒断导致埋大理石行为逐渐增加，直至48小时，在24小时间隔时达到峰值。在24小时间隔前30分钟给予亮丙瑞林（100 - 600微克/千克，皮下注射），剂量依赖性地降低了乙醇戒断诱导的埋大理石行为增加，且这种效果与氟西汀（15和30毫克/千克，腹腔注射）相当。此外，每天两次给予亮丙瑞林（50微克/千克，皮下注射），与乙醇同时给予，可防止乙醇戒断后埋大理石行为的逐渐增加，且这种效果与氟西汀（5毫克/千克，腹腔注射）相当。总之，长期给予乙醇后戒断会增加小鼠的埋大理石行为；亮丙瑞林可减弱其发展和表达。
