One year treatment with haloperidol or clozapine fails to alter neostriatal D1- and D2-dopamine receptor sensitivity in the rat

Charles R. Ashby; Robert Hitzemann; Joan E. Rubinstein; R. Y. Wang

doi:10.1016/0006-8993(89)91017-2

One year treatment with haloperidol or clozapine fails to alter neostriatal D₁- and D₂-dopamine receptor sensitivity in the rat

Charles R. Ashby, Robert Hitzemann, Joan E. Rubinstein, R. Y. Wang

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Rats were treated continuously with either haloperidol (HAL), clozapine (CLOZ) or tap water for one year. There were no differences between age-matched control and antipsychotic drug (APD) treated groups regarding the effects of the D₁-agonist (+)-SKF 38393 or the D₂-agonist quinpirole on striatal cAMP content. However, the combination of SKF (10 μM) and quinpirole (1 μM) produced a marked synergistic response in HAL-treated animals as compared to controls. Our data fail to support the hypothesis that APD produce their neurological side effects by inducing D₂-receptor hypersensitivity in the basal ganglia. However, the results do suggest that chronic APD treatment alters the interaction between D₁- and D₂-neostriatal receptors.

Original language	English (US)
Pages (from-to)	194-197
Number of pages	4
Journal	Brain research
Volume	493
Issue number	1
DOIs	https://doi.org/10.1016/0006-8993(89)91017-2
State	Published - Jul 24 1989
Externally published	Yes

Keywords

Antipsychotic drugs
Chronic drug treatment
Clozapine
Cyclic adenosine monophosphate
Dopamine receptor subtype
Haloperidol
Neostriatum
Supersensitivity

ASJC Scopus subject areas

Neuroscience(all)
Molecular Biology
Clinical Neurology
Developmental Biology

Access to Document

10.1016/0006-8993(89)91017-2

Cite this

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title = "One year treatment with haloperidol or clozapine fails to alter neostriatal D1- and D2-dopamine receptor sensitivity in the rat",

abstract = "Rats were treated continuously with either haloperidol (HAL), clozapine (CLOZ) or tap water for one year. There were no differences between age-matched control and antipsychotic drug (APD) treated groups regarding the effects of the D1-agonist (+)-SKF 38393 or the D2-agonist quinpirole on striatal cAMP content. However, the combination of SKF (10 μM) and quinpirole (1 μM) produced a marked synergistic response in HAL-treated animals as compared to controls. Our data fail to support the hypothesis that APD produce their neurological side effects by inducing D2-receptor hypersensitivity in the basal ganglia. However, the results do suggest that chronic APD treatment alters the interaction between D1- and D2-neostriatal receptors.",

keywords = "Antipsychotic drugs, Chronic drug treatment, Clozapine, Cyclic adenosine monophosphate, Dopamine receptor subtype, Haloperidol, Neostriatum, Supersensitivity",

author = "Ashby, {Charles R.} and Robert Hitzemann and Rubinstein, {Joan E.} and Wang, {R. Y.}",

note = "Funding Information: This work was supported by USPHS Grants MG-41440 and MH-00378 to R.Y.W., MH-00747 to J.E.R. and VA Res. Admin. to R.J.H. We thank Judith Shivak for typing the manuscript, Deyuan Jiang for her assistance with animal care and Dr. Joseph Schwartz for his assistance in data analysis. We also thank McNeil, Sandoz and Eli Lilly Laboratories for their generous supply of haloperidol, clozapine and quinpirole, respectively.",

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AU - Hitzemann, Robert

AU - Rubinstein, Joan E.

AU - Wang, R. Y.

N1 - Funding Information: This work was supported by USPHS Grants MG-41440 and MH-00378 to R.Y.W., MH-00747 to J.E.R. and VA Res. Admin. to R.J.H. We thank Judith Shivak for typing the manuscript, Deyuan Jiang for her assistance with animal care and Dr. Joseph Schwartz for his assistance in data analysis. We also thank McNeil, Sandoz and Eli Lilly Laboratories for their generous supply of haloperidol, clozapine and quinpirole, respectively.

PY - 1989/7/24

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N2 - Rats were treated continuously with either haloperidol (HAL), clozapine (CLOZ) or tap water for one year. There were no differences between age-matched control and antipsychotic drug (APD) treated groups regarding the effects of the D1-agonist (+)-SKF 38393 or the D2-agonist quinpirole on striatal cAMP content. However, the combination of SKF (10 μM) and quinpirole (1 μM) produced a marked synergistic response in HAL-treated animals as compared to controls. Our data fail to support the hypothesis that APD produce their neurological side effects by inducing D2-receptor hypersensitivity in the basal ganglia. However, the results do suggest that chronic APD treatment alters the interaction between D1- and D2-neostriatal receptors.

AB - Rats were treated continuously with either haloperidol (HAL), clozapine (CLOZ) or tap water for one year. There were no differences between age-matched control and antipsychotic drug (APD) treated groups regarding the effects of the D1-agonist (+)-SKF 38393 or the D2-agonist quinpirole on striatal cAMP content. However, the combination of SKF (10 μM) and quinpirole (1 μM) produced a marked synergistic response in HAL-treated animals as compared to controls. Our data fail to support the hypothesis that APD produce their neurological side effects by inducing D2-receptor hypersensitivity in the basal ganglia. However, the results do suggest that chronic APD treatment alters the interaction between D1- and D2-neostriatal receptors.

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