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    Pharmacol Biochem Behav. 2008 Oct;90(4):551-62.

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

    Mead A, Li M, Kapur S.

    Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE 685888, USA.

    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.

    PMID: 18547622 [PubMed - indexed for MEDLINE]

    PMCID: 2583124

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    Patient drug information

    • Haloperidol

      Haloperidol is used to treat psychotic disorders (conditions that cause difficulty telling the difference between things or ideas that are real and things or ideas that are not real). Haloperidol is also used to control ...

    • Clozapine (Clozaril®, FazaClo®)

      Clozapine is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions) in patients who have not been helped b...

    • Chlordiazepoxide (Librium®, Limbitrol®, Limbitrol® DS)

      Chlordiazepoxide is used to relieve anxiety and to control agitation caused by alcohol withdrawal.

    • » See all 4 drug reports ...