Abstract
Background
Based on the phenomenologic similarity between symptoms of drug withdrawal and the
negative symptoms of schizophrenia (e.g., anhedonia), we hypothesized that treatment
with clozapine may be effective against nicotine and amphetamine withdrawal.
Methods
A rate-independent discrete-trial threshold procedure was used to assess brain stimulation
reward in rats prepared with electrodes in the lateral hypothalamus. Somatic signs
of nicotine withdrawal were also assessed.
Results
Clozapine administration (.75 or 1.5 mg/kg) during nicotine or amphetamine withdrawal
did not affect the threshold elevations associated with drug withdrawal. The .75 mg/kg
clozapine dose reversed the increased number of somatic signs of nicotine withdrawal.
Ten days of clozapine treatment (3 mg/kg/b.i.d.) before exposure to nicotine prevented
the threshold elevations in a subset of rats and the increases in somatic signs in
all subjects. Fourteen-day pretreatment with clozapine (6 mg/kg/day) decreased the
duration of amphetamine withdrawal.
Conclusions
Correlational analyses indicated that the ability of clozapine to prevent the affective
aspects of drug withdrawal depended on low sensitivity to acute clozapine under baseline
conditions. The results are consistent with the clinical situation where clozapine
is partially effective against the negative symptoms of schizophrenia and more effective
in some individuals than others. These results indicate that lack of sensitivity to
the initial negative effects of clozapine may predict its a subsequent therapeutic
response. Finally, the data suggest that there may be commonalities in the neurosubstrates
mediating affective aspects of drug withdrawal and the negative symptoms of schizophrenia.
Keywords
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Article info
Publication history
Accepted:
February 13,
2003
Received in revised form:
February 6,
2003
Received:
September 2,
2002
Identification
Copyright
© 2003 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
