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Effect of chronic treatment with typical and atypical neuroleptics on the expression of dopamine D2 and D3 receptors in rat brain

Effect of chronic treatment with typical and atypical neuroleptics on the expression of dopamine D2 and D3 receptors in rat brain
Effect of chronic treatment with typical and atypical neuroleptics on the expression of dopamine D2 and D3 receptors in rat brain

The effect of chronic treatment (21 days) with typical and atypical neuroleptics on the expression of striatal and limbic D2 and D3 dopamine receptors was investigated in rat brain by in situ hybridization and receptor autoradiography. Haloperidol and sulpiride increased D2 receptor expression in striatal and limbic areas. In contrast, clozapine had no effect on D2 receptor expression. Haloperidol decreased D3 receptor expression in limbic areas, with the exception of the islands of Calleja where an increase occurred. Sulpiride and clozapine increased D3 receptor expression in limbic and striatal regions but decreased D3 receptor expression in the islands of Calleja. This study demonstrates that chronic treatment with typical and atypical neuroleptics produces different regionally specific changes in limbic and striatal D2 and D3 receptor expression. The alterations in dopamine receptor expression were different for each drug, but a distinction between the effects of atypical and typical neuroleptics could be made. Comparison of mRNA levels in animals which were not withdrawn from drug treatment with those that were withdrawn, demonstrated that some changes in receptor expression occurred during drug treatment, whilst others only manifested when drug treatment had ceased. The different regulation of dopamine D2 and D3 receptor expression by typical and atypical neuroleptics may have relevance to the ability of these drugs to cause extrapyramidal side-effects.

Animals, Antipsychotic Agents, Clozapine, Haloperidol, In Situ Hybridization, Limbic System, Male, Neostriatum, RNA, Messenger, Rats, Rats, Sprague-Dawley, Receptors, Dopamine D2, Receptors, Dopamine D3, Sulpiride, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
0033-3158
362-70
Hurley, Michael J.
07b0180f-8e32-4ce1-8185-e046a42ef15a
Stubbs, Carole M.
1f1b9c08-92b5-41b8-80e9-8c0f26e41544
Jenner, Peter
785c25df-ec64-4181-b057-26dd31cd9d84
Marsden, C. David
a3e9f672-aa75-4109-a1d5-6d0740e56220
Hurley, Michael J.
07b0180f-8e32-4ce1-8185-e046a42ef15a
Stubbs, Carole M.
1f1b9c08-92b5-41b8-80e9-8c0f26e41544
Jenner, Peter
785c25df-ec64-4181-b057-26dd31cd9d84
Marsden, C. David
a3e9f672-aa75-4109-a1d5-6d0740e56220

Hurley, Michael J., Stubbs, Carole M., Jenner, Peter and Marsden, C. David (1996) Effect of chronic treatment with typical and atypical neuroleptics on the expression of dopamine D2 and D3 receptors in rat brain. Psychopharmacology, 128 (4), 362-70. (doi:10.1007/s002130050146 .).

Record type: Article

Abstract

The effect of chronic treatment (21 days) with typical and atypical neuroleptics on the expression of striatal and limbic D2 and D3 dopamine receptors was investigated in rat brain by in situ hybridization and receptor autoradiography. Haloperidol and sulpiride increased D2 receptor expression in striatal and limbic areas. In contrast, clozapine had no effect on D2 receptor expression. Haloperidol decreased D3 receptor expression in limbic areas, with the exception of the islands of Calleja where an increase occurred. Sulpiride and clozapine increased D3 receptor expression in limbic and striatal regions but decreased D3 receptor expression in the islands of Calleja. This study demonstrates that chronic treatment with typical and atypical neuroleptics produces different regionally specific changes in limbic and striatal D2 and D3 receptor expression. The alterations in dopamine receptor expression were different for each drug, but a distinction between the effects of atypical and typical neuroleptics could be made. Comparison of mRNA levels in animals which were not withdrawn from drug treatment with those that were withdrawn, demonstrated that some changes in receptor expression occurred during drug treatment, whilst others only manifested when drug treatment had ceased. The different regulation of dopamine D2 and D3 receptor expression by typical and atypical neuroleptics may have relevance to the ability of these drugs to cause extrapyramidal side-effects.

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More information

Published date: December 1996
Keywords: Animals, Antipsychotic Agents, Clozapine, Haloperidol, In Situ Hybridization, Limbic System, Male, Neostriatum, RNA, Messenger, Rats, Rats, Sprague-Dawley, Receptors, Dopamine D2, Receptors, Dopamine D3, Sulpiride, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 416140
URI: http://eprints.soton.ac.uk/id/eprint/416140
ISSN: 0033-3158
PURE UUID: 8dbf1cc6-36a8-4948-8b52-172eb2d23b24

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Date deposited: 06 Dec 2017 17:30
Last modified: 15 Mar 2024 17:13

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Contributors

Author: Michael J. Hurley
Author: Carole M. Stubbs
Author: Peter Jenner
Author: C. David Marsden

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