Does Antagonism at 5-HT2A Receptors Potentiate D-2 Blockade-Induced Disruption of Conditioned Avoidance Response?

doi:10.1037/pha0000243

	Does Antagonism at 5-HT2A Receptors Potentiate D-2 Blockade-Induced Disruption of Conditioned Avoidance Response?
	Gao, Jun1,2,3 ; Huang, Yujing 1,2; Li, Ming 1,4
通讯作者	Gao, Jun(gaojunscience@126.com) ; Li, Ming(mli2@unl.edu)
摘要	Existing evidence in the literature shows that antagonism at 5-HT2A receptors potentiates D-2 antagonism-induced disruption of conditioned avoidance response (CAR), a behavioral index of antipsychotic activity, suggesting that combining 5-HT2A antagonism with D-2 antagonism may confer an enhanced antipsychotic effect. The present study reexamined this issue and further investigated other behavioral effects of drug-drug interaction, mainly the conditioned drug effect (via drug-drug conditioning) and 5-HT2A antagonism's modulation on antipsychotic-induced sensitization (an enhanced avoidance disruption). Well-trained adult male Sprague-Dawley rats were first repeatedly tested for 7 days under haloperidol (HAL; 0.05 mg/kg, subcutaneous [sc], a typical antipsychotic drug with potent D-2 antagonism), MDL100907 (0.5 and 1.0 mg/kg, sc, a selective 5-HT2A antagonist), combined MDL100907 and HAL, or vehicle control, followed by one challenge test under MDL100907 (0.5 mg/kg) to assess the conditioned drug effect and one challenge test under HAL (0.025 mg/kg) to assess HAL sensitization. Results showed that MDL100907 by itself had no effect on CAR. Importantly, MDL100907 treatment did little to alter the acute and sensitized effects of HAL-induced (0.05 mg/kg, sc) suppression of CAR under various treatment conditions. Repeated pairing of MDL100907 (1.0 mg/kg) with HAL rendered MDL100907 itself to exhibit an "acquired" CAR disruptive effect through a drug-drug conditioning process. These results do not support the notion that 5-HT2A receptor blockade enhances the antipsychotic-like effects of typical antipsychotic drugs, although they do highlight the importance of drug-drug conditioning process in altering drug efficacy in polypharmacy.
关键词	conditioned avoidance response MDL100907 haloperidol drug-drug conditioning schizophrenia
	2019-04-01
语种	英语
DOI	10.1037/pha0000243
发表期刊	EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY
ISSN	1064-1297
卷号	27 期号:2 页码:103-108
收录类别	SCI ; SCI
资助项目	National Natural Science Foundation of China[31500891] ; Fundamental Research Funds for the Central Universities[SWU1609131] ; Fundamental Research Funds for the Central Universities[SWU115030] ; Fundamental Research Funds for the Central Universities[SWU116014] ; Chinese Academy of Sciences Key Laboratory of Mental Health, Institute of Psychology[KLMH2016G03] ; Chongqing Collaborative Innovation Center for Brain Science, China
出版者	AMER PSYCHOLOGICAL ASSOC
WOS关键词	ANTIPSYCHOTIC-DRUGS ; HALOPERIDOL ; BEHAVIOR ; RATS ; SENSITIZATION ; ENHANCEMENT ; ATTENUATION ; RITANSERIN ; OLANZAPINE ; RACLOPRIDE
WOS研究方向	Psychology ; Pharmacology & Pharmacy ; Psychiatry
WOS类目	Psychology, Biological ; Psychology, Clinical ; Pharmacology & Pharmacy ; Psychiatry
WOS记录号	WOS:000462868100001
资助机构	National Natural Science Foundation of China ; Fundamental Research Funds for the Central Universities ; Chinese Academy of Sciences Key Laboratory of Mental Health, Institute of Psychology ; Chongqing Collaborative Innovation Center for Brain Science, China
引用统计
文献类型	期刊论文
条目标识符	http://ir.psych.ac.cn/handle/311026/28963
专题	中国科学院心理健康重点实验室
通讯作者	Gao, Jun; Li, Ming
作者单位	1.Southwest Univ, Fac Psychol, 2 Tiansheng Rd, Chongqing 400715, Peoples R China 2.Southwest Univ, Key Lab Cognit & Personal, 2 Tiansheng Rd, Chongqing 400715, Peoples R China 3.Chinese Acad Sci, Key Lab Mental Hlth, Inst Psychol, Beijing, Peoples R China 4.Univ Nebraska, Dept Psychol, 238 Burnett Hall, Lincoln, NE 68588 USA
第一作者单位	中国科学院心理健康重点实验室
通讯作者单位	中国科学院心理健康重点实验室
推荐引用方式 GB/T 7714	Gao, Jun,Huang, Yujing,Li, Ming. Does Antagonism at 5-HT2A Receptors Potentiate D-2 Blockade-Induced Disruption of Conditioned Avoidance Response?[J]. EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY,2019,27(2):103-108.
APA	Gao, Jun,Huang, Yujing,&Li, Ming.(2019).Does Antagonism at 5-HT2A Receptors Potentiate D-2 Blockade-Induced Disruption of Conditioned Avoidance Response?.EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY,27(2),103-108.
MLA	Gao, Jun,et al."Does Antagonism at 5-HT2A Receptors Potentiate D-2 Blockade-Induced Disruption of Conditioned Avoidance Response?".EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY 27.2(2019):103-108.