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Avoidance disruptive effect of clozapine and olanzapine is potentiated by increasing the test trials: Further test of the motivational salience hypothesis
Feng, Min1,2,3; Sui, Nan1; Li, Ming2; Sui, N (reprint author), Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China.
2013
Source PublicationPHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
ISSN0191-8869
Subtype期刊论文
Volume103Issue:3Pages:467-473
Contribution Rank1
AbstractAntipsychotic drugs suppress animals' ability to avoid an aversive stimulus in the conditioned avoidance response model (CAR). This behavioral effect is thought to reflect antipsychotic activity and is suggested to be mediated by a drug's action in attenuating the motivational salience of a conditioned stimulus (CS). In the present study, we tested whether atypical antipsychotic drugs clozapine and olanzapine act through this behavioral mechanism by manipulating the number of avoidance test trials. We reasoned that more CS trials in the presence of clozapine or olanzapine would afford the drug more opportunities to decrease the motivational salience of the CS, thus avoidance decline would be greater with the increase of CS trials in each test session. In two separate experiments, adult male Sprague-Dawley rats were tested under clozapine (5.0 mg/kg, sc), olanzapine (0.5 mg/kg, sc) or vehicle (sterile water) for 6 consecutive days in three CS trial conditions (i.e. 3, 10, and 40 CS trials per session). Two days later, all rats were tested under the same 40-trial session after receiving clozapine (5.0 mg/kg, sc) or olanzapine (0.5 mg/kg, sc). Results show that repeated clozapine and olanzapine treatment persistently decreased avoidance response, and this effect was potentiated by the increase of number of CS trials in the test sessions, as the clozapine-treated or olanzapine-treated rats tested under the 40-trial or 10-trial condition had significantly lower avoidance and faster decline across-sessions than those tested under the 3-trial condition. This potentiated effect was not only seen in the total avoidance percentage, but also observed in the within-session decline pattern in the last three drug test sessions and in the final 40-trial test session. These findings suggest that the clinical efficacy of a drug can be enhanced by increasing the exposure of symptoms in the presence of the drug. (c) 2012 Elsevier Inc. All rights reserved.
KeywordClozapine Olanzapine Conditioned avoidance response Motivational salience Within-session decline
Subject AreaPersonality Psychology
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Indexed BySCI
Language英语
Funding OrganizationNIMH grant [R01MH085635]
Project Intro.This study was funded by the NIMH grant (R01MH085635) to Professor Ming Li.
WOS Research AreaBehavioral Sciences ; Neurosciences & Neurology ; Pharmacology & Pharmacy
WOS SubjectBehavioral Sciences ; Neurosciences ; Pharmacology & Pharmacy
WOS IDWOS:000314792100007
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS KeywordANTIPSYCHOTIC-DRUGS ; LINKING BIOLOGY ; TIME-COURSE ; IN-VIVO ; DOPAMINE ; CHLORPROMAZINE ; RATS ; SCHIZOPHRENIA ; PSYCHOSIS ; PHARMACOLOGY
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Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/10706
Collection中国科学院心理健康重点实验室
Corresponding AuthorSui, N (reprint author), Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China.
Affiliation1.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China
2.Univ Nebraska, Dept Psychol, Lincoln, NE 68588 USA
3.Chinese Acad Sci, Grad Sch, Beijing 100101, Peoples R China
First Author AffilicationKey Laboratory of Mental Health, CAS
Recommended Citation
GB/T 7714
Feng, Min,Sui, Nan,Li, Ming,et al. Avoidance disruptive effect of clozapine and olanzapine is potentiated by increasing the test trials: Further test of the motivational salience hypothesis[J]. PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR,2013,103(3):467-473.
APA Feng, Min,Sui, Nan,Li, Ming,&Sui, N .(2013).Avoidance disruptive effect of clozapine and olanzapine is potentiated by increasing the test trials: Further test of the motivational salience hypothesis.PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR,103(3),467-473.
MLA Feng, Min,et al."Avoidance disruptive effect of clozapine and olanzapine is potentiated by increasing the test trials: Further test of the motivational salience hypothesis".PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR 103.3(2013):467-473.
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