NDLI: Clozapine and olanzapine exhibit an intrinsic anxiolytic property in two conditioned fear paradigms: contrast with haloperidol and chlordiazepoxide.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Mead, Alexa Li, Ming Kapur, Shitij
Description	Country affiliation: United States Author Affiliation: Mead A ( Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE 685888, USA.)
Abstract	Psychotic fear and anxiety disturbances are seen at a relatively high frequency in patients with schizophrenia. Atypical anti-psychotics are believed to show superior efficacy in reducing these symptoms. However, clinical and preclinical evidence regarding their anxiolytic efficacy has been mixed. In this study, we evaluated the possible anxiolytic property of two atypicals clozapine and olanzapine and compared them with typical haloperidol and chlordiazepoxide (a prototype of sedative-anxiolytic drug) in two preclinical models of fear. In Experiment 1, we used a fear-induced passive avoidance and conditioned place aversion paradigm and examined the effects of clozapine (20 mg/kg, sc), haloperidol (0.05 mg/kg, sc) and chlordiazepoxide (10 mg/ kg, ip). In Experiments 2 and 3, we used a two-way active avoidance conditioning paradigm and further compared the effects of clozapine (20 mg/kg, sc), haloperidol (0.05 mg/kg, sc), chlordiazepoxide (10 mg/kg, ip) and three doses of olanzapine (0.5, 1.0, and 2.0 mg/kg, sc). Results show that clozapine and chlordiazepoxide, but not haloperidol, significantly attenuated the shock conditioning-induced place aversion, decreased the amount of defecations and the number of the 22-kHz vocalizations. Clozapine also reduced the shock conditioning-induced hyperthermia. Similar to clozapine, olanzapine also significantly decreased the amount of defecations and reduced the shock conditioning-induced hyperthermia, but it did not inhibit the 22-kHz vocalizations. This study demonstrates that clozapine and olanzapine possess an intrinsic anxiolytic property, which is not attributable to its superior anti-'psychotic' effect or its favorable effects on motor functions or learning and memory processes. These findings also suggest that the combined use of passive avoidance and active avoidance conditioning models can be useful in better differentiating typical and atypical anti-psychotics as well as anxiolytics.
File Format	HTM / HTML
ISSN	00913057
e-ISSN	18735177
DOI	10.1016/j.pbb.2008.04.014
Journal	Pharmacology Biochemistry and Behavior
Issue Number	4
Volume Number	90
Language	English
Publisher	Elsevier
Publisher Date	2008-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Behavioral Sciences Discipline Biochemistry Discipline Pharmacology Anti-anxiety Agents Antipsychotic Agents Therapeutic Use Benzodiazepines Chlordiazepoxide Pharmacology Clozapine Conditioning (psychology) Drug Effects Psychology Haloperidol Hypnotics And Sedatives Animals Avoidance Learning Dose-response Relationship, Drug Motor Activity Rats, Sprague-dawley Receptors, Dopamine D2 Vocalization, Animal Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Biological Psychiatry Behavioral Neuroscience Biochemistry Clinical Biochemistry Toxicology Pharmacology

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Clozapine and Olanzapine Exhibit an Intrinsic Anxiolytic Property in Two Conditioned Fear Paradigms: Contrast with Haloperidol and Chlordiazepoxide

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Clozapine and Olanzapine Exhibit an Intrinsic Anxiolytic Property in Two Conditioned Fear Paradigms: Contrast with Haloperidol and Chlordiazepoxide

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