Roles of 5-HT2 receptors in effects of DOM,ketamine and methamphetamine on prepulse inhibition in Sprague Dawley rats  

作　　者：JIANG Kai-li LI Kai-xi LIU Xiao-yan SU Rui-bin 

机构地区：[1]State Key Laboratory of Toxicology and Medical Countermeasures,Beijing Key Laboratory of Neu-ropsychopharmacology,Beijing Institute of Phar-macology and Toxicology,Beijing 100850,China [2]Key Laboratory of Xinjiang Phytomedicine Resource and Utilization,Ministry of Education,Department of Pharmacology,Shihezi University,Shihezi 832003,China

出　　处：《中国药理学与毒理学杂志》2021年第9期669-670,共2页Chinese Journal of Pharmacology and Toxicology

摘　　要：OBJECTIVE Prepulse inhibition(PPI)of the acoustic startle response provides a measure of sensorimotor gating system mecha⁃nisms,which is known to be impaired in schizo⁃phrenia patients.We assessed the effects of the 5-HT2A/2C receptor agonist(±)2,5-dimethoxy-4-methylamphetamine(DOM),the NMDA receptor antagonist ketamine,the dopamine receptor ago⁃nist methamphetamine(Meth)on PPI and the startle magnitude in SD rats.METHODS AND RESULTS Systemic administration of the three compounds all dose-dependently reduced PPI.However,as far as startle magnitude,only DOM at the doses of 3 mg·kg-1 reduced that,while both ketamine and Meth did not change the startle magnitudes.Furthermore,to determine whether 5-HT2A receptor mediate this effect,the non-spe⁃cific 5-HT2 receptor antagonist cyproheptadine,specific 5-HT2A receptor antagonist ketanserin and specific 5-HT2C receptor antagonist SB242084 were tested.Cyproheptadine,ketan⁃serin and SB242084 did not alter startle ampli⁃tude by themselves in SD rats and only ketanserin slightly increased PPI at higher dose(3 mg·kg-1).PPI impairment induced by DOM was restored by pretreatment of cyproheptadine(1 mg·kg-1)and ketanserin(1 mg·kg-1),while not by pretreat⁃ment of SB242084(1 mg·kg-1).Damage of PPI induced by ketamine and Meth was not reversed by cyproheptadine(1 and 5 mg·kg-1).CONCLU⁃SION The receptor mechanisms underlying the disruption of PPI caused by DOM,ketamine and Meth were different from each other,at least 5-HT2A receptor was not the junction receptor for which the three chemicals acted.

关 键 词：prepulse inhibition 5-HT2 receptor startle magnitude psychoactive substances 

分 类 号：R965[医药卫生—药理学]