Contrasting Effects of Chronic Clozapine, SeroquelTM (ICI 204,636) and Haloperidol Administration on ΔFosB-like Immunoreactivity in the Rodent Forebrain

F. Vahid-Ansari, Yusaku Nakabeppu, G. S. Robertson

研究成果: ジャーナルへの寄稿記事

46 引用 (Scopus)

抄録

We have recently demonstrated that specific neuroanatomical patterns of Fos-like immunoreactivity are predictive of atypical antipsychotic activity. However, the fact that neuroleptics must be administered chronically in order to generate both extrapyramidal side effects and an optimal therapeutic response calls into question the relevance of acute changes in Fos-like immunoreactivity for these slowly developing events. Fos-like immunoreactivity cannot be used to identify neurons activated by chronic neuroleptic administration because the increase in Fos-like immunoreactivity produced by an acute antipsychotic injection is dramatically reduced following repeated neuroleptic administration. In contrast, expression of the immediate-early gene product ΔFosB is persistently elevated in the striatum by chronic haloperidol administration. This suggests that ΔFosB-like immunoreactivity may be used to identify neurons activated by chronic antipsychotic administration. Since typical and atypical neuroleptics elevate Fos-like immunoreactivity in different regions of the forebrain acutely, the purpose of the present study was to determine whether typical (haloperidol) and atypical (clozapine, ICI 204,636) antipsychotics produce distinct patterns of elevated ΔFosB-like immunoreactivity in the forebrain after chronic administration. Administration of haloperidol (2 mg/kg/day) to rats for 19 days induced a homogeneous elevation of neurons which displayed ΔFosB-like immunoreactivity in the ventral, medial and dorsolateral aspects of the striatum. Chronic haloperidol administration did not enhance ΔFosB-like immunoreactivity in the prefrontal cortex and lateral septal nucleus. Repeated administration of clozapine (20 mg/kg/day) and ICI 204,636 (20 mg/kg/day) for 19 days elevated ΔFosB-like immunoreactivity not only in the ventral striatum but also in the prefrontal cortex and lateral septal nucleus. However, these compounds had weak effects on ΔFosB-like immunoreactivity in the dorsolateral striatum. These results suggest that a preferential action on limbic structures such as the prefrontal cortex, ventral striatum and lateral septal nucleus may account for the ability of chronic clozapine and ICI 204,636 administration to reduce the symptoms of schizophrenia without generating extrapyramidal side effects.
元の言語英語
ページ(範囲)927-936
ページ数15
ジャーナルEuropean Journal of Neuroscience
8
発行部数5
DOI
出版物ステータス出版済み - 5 1 1996

Fingerprint

Clozapine
Haloperidol
Prosencephalon
Antipsychotic Agents
Rodentia
Septal Nuclei
Prefrontal Cortex
Neurons
Immediate-Early Genes
Aptitude
Quetiapine Fumarate
Therapeutic Uses
Schizophrenia
Injections

これを引用

Contrasting Effects of Chronic Clozapine, SeroquelTM (ICI 204,636) and Haloperidol Administration on ΔFosB-like Immunoreactivity in the Rodent Forebrain. / Vahid-Ansari, F.; Nakabeppu, Yusaku; Robertson, G. S. .

:: European Journal of Neuroscience, 巻 8, 番号 5, 01.05.1996, p. 927-936.

研究成果: ジャーナルへの寄稿記事

@article{559b70fef8f844b481e987e7af03ac7f,
title = "Contrasting Effects of Chronic Clozapine, SeroquelTM (ICI 204,636) and Haloperidol Administration on ΔFosB-like Immunoreactivity in the Rodent Forebrain",
abstract = "We have recently demonstrated that specific neuroanatomical patterns of Fos-like immunoreactivity are predictive of atypical antipsychotic activity. However, the fact that neuroleptics must be administered chronically in order to generate both extrapyramidal side effects and an optimal therapeutic response calls into question the relevance of acute changes in Fos-like immunoreactivity for these slowly developing events. Fos-like immunoreactivity cannot be used to identify neurons activated by chronic neuroleptic administration because the increase in Fos-like immunoreactivity produced by an acute antipsychotic injection is dramatically reduced following repeated neuroleptic administration. In contrast, expression of the immediate-early gene product ΔFosB is persistently elevated in the striatum by chronic haloperidol administration. This suggests that ΔFosB-like immunoreactivity may be used to identify neurons activated by chronic antipsychotic administration. Since typical and atypical neuroleptics elevate Fos-like immunoreactivity in different regions of the forebrain acutely, the purpose of the present study was to determine whether typical (haloperidol) and atypical (clozapine, ICI 204,636) antipsychotics produce distinct patterns of elevated ΔFosB-like immunoreactivity in the forebrain after chronic administration. Administration of haloperidol (2 mg/kg/day) to rats for 19 days induced a homogeneous elevation of neurons which displayed ΔFosB-like immunoreactivity in the ventral, medial and dorsolateral aspects of the striatum. Chronic haloperidol administration did not enhance ΔFosB-like immunoreactivity in the prefrontal cortex and lateral septal nucleus. Repeated administration of clozapine (20 mg/kg/day) and ICI 204,636 (20 mg/kg/day) for 19 days elevated ΔFosB-like immunoreactivity not only in the ventral striatum but also in the prefrontal cortex and lateral septal nucleus. However, these compounds had weak effects on ΔFosB-like immunoreactivity in the dorsolateral striatum. These results suggest that a preferential action on limbic structures such as the prefrontal cortex, ventral striatum and lateral septal nucleus may account for the ability of chronic clozapine and ICI 204,636 administration to reduce the symptoms of schizophrenia without generating extrapyramidal side effects.",
author = "F. Vahid-Ansari and Yusaku Nakabeppu and Robertson, {G. S.}",
year = "1996",
month = "5",
day = "1",
doi = "10.1111/j.1460-9568.1996.tb01579.x",
language = "English",
volume = "8",
pages = "927--936",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Contrasting Effects of Chronic Clozapine, SeroquelTM (ICI 204,636) and Haloperidol Administration on ΔFosB-like Immunoreactivity in the Rodent Forebrain

AU - Vahid-Ansari, F.

AU - Nakabeppu, Yusaku

AU - Robertson, G. S.

PY - 1996/5/1

Y1 - 1996/5/1

N2 - We have recently demonstrated that specific neuroanatomical patterns of Fos-like immunoreactivity are predictive of atypical antipsychotic activity. However, the fact that neuroleptics must be administered chronically in order to generate both extrapyramidal side effects and an optimal therapeutic response calls into question the relevance of acute changes in Fos-like immunoreactivity for these slowly developing events. Fos-like immunoreactivity cannot be used to identify neurons activated by chronic neuroleptic administration because the increase in Fos-like immunoreactivity produced by an acute antipsychotic injection is dramatically reduced following repeated neuroleptic administration. In contrast, expression of the immediate-early gene product ΔFosB is persistently elevated in the striatum by chronic haloperidol administration. This suggests that ΔFosB-like immunoreactivity may be used to identify neurons activated by chronic antipsychotic administration. Since typical and atypical neuroleptics elevate Fos-like immunoreactivity in different regions of the forebrain acutely, the purpose of the present study was to determine whether typical (haloperidol) and atypical (clozapine, ICI 204,636) antipsychotics produce distinct patterns of elevated ΔFosB-like immunoreactivity in the forebrain after chronic administration. Administration of haloperidol (2 mg/kg/day) to rats for 19 days induced a homogeneous elevation of neurons which displayed ΔFosB-like immunoreactivity in the ventral, medial and dorsolateral aspects of the striatum. Chronic haloperidol administration did not enhance ΔFosB-like immunoreactivity in the prefrontal cortex and lateral septal nucleus. Repeated administration of clozapine (20 mg/kg/day) and ICI 204,636 (20 mg/kg/day) for 19 days elevated ΔFosB-like immunoreactivity not only in the ventral striatum but also in the prefrontal cortex and lateral septal nucleus. However, these compounds had weak effects on ΔFosB-like immunoreactivity in the dorsolateral striatum. These results suggest that a preferential action on limbic structures such as the prefrontal cortex, ventral striatum and lateral septal nucleus may account for the ability of chronic clozapine and ICI 204,636 administration to reduce the symptoms of schizophrenia without generating extrapyramidal side effects.

AB - We have recently demonstrated that specific neuroanatomical patterns of Fos-like immunoreactivity are predictive of atypical antipsychotic activity. However, the fact that neuroleptics must be administered chronically in order to generate both extrapyramidal side effects and an optimal therapeutic response calls into question the relevance of acute changes in Fos-like immunoreactivity for these slowly developing events. Fos-like immunoreactivity cannot be used to identify neurons activated by chronic neuroleptic administration because the increase in Fos-like immunoreactivity produced by an acute antipsychotic injection is dramatically reduced following repeated neuroleptic administration. In contrast, expression of the immediate-early gene product ΔFosB is persistently elevated in the striatum by chronic haloperidol administration. This suggests that ΔFosB-like immunoreactivity may be used to identify neurons activated by chronic antipsychotic administration. Since typical and atypical neuroleptics elevate Fos-like immunoreactivity in different regions of the forebrain acutely, the purpose of the present study was to determine whether typical (haloperidol) and atypical (clozapine, ICI 204,636) antipsychotics produce distinct patterns of elevated ΔFosB-like immunoreactivity in the forebrain after chronic administration. Administration of haloperidol (2 mg/kg/day) to rats for 19 days induced a homogeneous elevation of neurons which displayed ΔFosB-like immunoreactivity in the ventral, medial and dorsolateral aspects of the striatum. Chronic haloperidol administration did not enhance ΔFosB-like immunoreactivity in the prefrontal cortex and lateral septal nucleus. Repeated administration of clozapine (20 mg/kg/day) and ICI 204,636 (20 mg/kg/day) for 19 days elevated ΔFosB-like immunoreactivity not only in the ventral striatum but also in the prefrontal cortex and lateral septal nucleus. However, these compounds had weak effects on ΔFosB-like immunoreactivity in the dorsolateral striatum. These results suggest that a preferential action on limbic structures such as the prefrontal cortex, ventral striatum and lateral septal nucleus may account for the ability of chronic clozapine and ICI 204,636 administration to reduce the symptoms of schizophrenia without generating extrapyramidal side effects.

U2 - 10.1111/j.1460-9568.1996.tb01579.x

DO - 10.1111/j.1460-9568.1996.tb01579.x

M3 - Article

C2 - 8743740

VL - 8

SP - 927

EP - 936

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 5

ER -