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KMID : 0350519950480041031
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Journal of Catholic Medical College
1995 Volume.48 No. 4 p.1031 ~ p.1045
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Expression of c-fos in Rat Brain Induced by Typical and Atypical Antipsychotics
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Abstract
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Proto-oncogene c-fos is known to encode a 62 kDa nuclear protein (Fos) which, after translation in the cytoplasm, re-enters the nucleus and binds to DNA. Since c-fos can be activated in the central nervous system by a variety of physiological and
pharmacological treatments, it has been proposed that Fos immunohistochemistry might be useful in identifying brain regions that constitute the pharmacological target areas for antipsychotics. The mechanism by which the atypical antipsychotics
produce
their therapeutic effects in the treatment of schiophrenia, both positive and negative symptom types, without causing the extrapyramidal symptoms that are characteristic of most typical antipsychotics remains to be clarified.
The present animal experimentation has been undertaken to investigate the effects of typical and atypical antipsychotic drugs in the brain. We investigated the brain. We investigated the differences between potential neuroanatomical sites of
action
of
(1) two typical antipsychotics (chlorpromazine, haloperidol), (2) three atypical antipsychotics (clozapine, risperidone, ritanserin), and (3) a combination of both typical and atypical antipsychotics (haloperidol+ritanserin) by comparing thfir
effects
on c-fos expression in the medial prefrontal cortex, nucleus accumbens, and lateral striatum of the rat brain.
Seventy-two healthy Wistar rats of male sex, weighing 300-450g, were divided into 12 groups according to the type and amount of the agents tested [vehicle (0.14 M acetic acid] ml/kg), chlorpromazine (10 mg/kg and 25 mg/kg), haloperidol (0.5 mg/kg
and 1
mg/kg), clozapine (20 mg/kg and 30 mg/kg), risperidone (0.5 mg/kg and 1 mg/kg), ritanserin (4 mg/kg and 6 mg/kg), haloperidol + ritanserin (1 mg/kg+4 mg/kg)]. The brain of variously treated rat was examined after 2 hours immunohistochemically.
The
brain
was removed immediately after perfusion with 4 % paraformaldehyde and piaced in a fresh fixative of the same solution. After 12-hr fixation, brain sections (30μm) of the areas including the medial prefrontal cortex, nucleus accumbens, and
lateral
striatum were stained by Fos immunohistochemistry, and subjected to light microscopic analytical observations.
@ES The results were as follows :
@EN (1) The number of Fos-positive neurons in the medial prefrontal cortex was significantly increased in the clozapine, risperidone, and ritanserin treated groups than in the control group (P<0.05).
(2) The number of Fos-positive neurons in the nucleus accumbens was significantly increased in the chlorpromazine (25 mg/kg), haloperidol, cloapine, and risperidone treated groups than in the control group (P<0.05).
(3) The number of Fos-positive neurons in the lateral striatum was significantly increased in the chlorpromazine, haloperidol, and risperidone treated groups than in the control group (P<0.05).
(4) The number of Fos-positive neurons in the medial prefrontal cortex, nucleus accumbens, and lateral striatum was not significantly different between the combined haloperidol and ritanserin treated group and the risperidone (1 mg/kg) treatfed
group.
These results suggest that the unique therapeutic effects of clozapine, risperidone, and ritanserin on negative symptoms with relatively low extrapyramidal symptoms in schizophrenia are probably related to pharmacologic action that involves the
medial
prefrontal cortex more predominantly than lateral striatum.
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KEYWORD
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