Blunting of the neurotensin mRNA response to haloperidol in the striatum of aging rats: possible relationship to decline in dopamine D2 receptor expression

Dorcas J. Dobie; Kalpana M. Merchant; Mark W. Hamblin; Govind T. Vatassery; Maurice W. Dysken; Daniel M. Dorsa

doi:10.1016/0006-8993(93)90198-V

Blunting of the neurotensin mRNA response to haloperidol in the striatum of aging rats: possible relationship to decline in dopamine D2 receptor expression

Dorcas J. Dobie, Kalpana M. Merchant, Mark W. Hamblin, Govind T. Vatassery, Maurice W. Dysken, Daniel M. Dorsa

Psychiatry & Behavioral Sciences

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Abstract

Neuroleptic drugs such as haloperidol (H) induce a rapid increase in neurotensin/neuromedin N (NT/N) gene expression in the dorsolateral striatum (DLSt) and nucleus accumbens (NA) in young adult rats. This effect may be mediated by post-receptor effectors that are activated by dopamine D2 receptor antagonism. The regional pattern of induction of neurotensin gene expression correlates with the side effect profile of particular neuroleptics. As motor side effects of H differ in aged animals, we hypothesized that the regional expression of the neurotensin gene may differ between young and old animals. We administered H or saline acutely to 3, 14, and 25 month-old Fischer 344 rats, followed by in situ hybridization and quantitative autradiography for NT/N mRNA. There was a significant age effect on the H-induced NT/N mRNA response in the DLSt, but not the NA, of older animals. In addition to the blunted NT/N mRNA response, significant decreases in D2 receptor mRNA were observed in the lateral striatum of another group of young, middle-aged, and aged rats. Age-related blunting of the NT/N mRNA response to H in the DLSt may be due in part to a decrease in D2 receptors in this structure.

Original language	English (US)
Pages (from-to)	105-113
Number of pages	9
Journal	Brain Research
Volume	616
Issue number	1-2
DOIs	https://doi.org/10.1016/0006-8993(93)90198-V
State	Published - Jul 9 1993

Bibliographical note

Funding Information:
Acknowledgements. This work was supported by NARSAD (DJD), by NIA Geriatric Academic Program AG 00503 (DJD), by Scottish Rite Schizophrenia Research Program (KMM, DMD), by the Washington Institute for Mental Illness Research (KMM, DMD), by NIH Grant NS20311 (DMD) and by the Department of Veteran's Affairs (DMD, MWH). We are grateful for the technical assistance of Anne Kalliomaki, Carl Sikkema, and Lori Holden.

Keywords

Aging
Dopamine receptor
Fischer 344
Haloperidol
In situ hybridization
Neurotensin
Nucleus accumbens
Striatum

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title = "Blunting of the neurotensin mRNA response to haloperidol in the striatum of aging rats: possible relationship to decline in dopamine D2 receptor expression",

abstract = "Neuroleptic drugs such as haloperidol (H) induce a rapid increase in neurotensin/neuromedin N (NT/N) gene expression in the dorsolateral striatum (DLSt) and nucleus accumbens (NA) in young adult rats. This effect may be mediated by post-receptor effectors that are activated by dopamine D2 receptor antagonism. The regional pattern of induction of neurotensin gene expression correlates with the side effect profile of particular neuroleptics. As motor side effects of H differ in aged animals, we hypothesized that the regional expression of the neurotensin gene may differ between young and old animals. We administered H or saline acutely to 3, 14, and 25 month-old Fischer 344 rats, followed by in situ hybridization and quantitative autradiography for NT/N mRNA. There was a significant age effect on the H-induced NT/N mRNA response in the DLSt, but not the NA, of older animals. In addition to the blunted NT/N mRNA response, significant decreases in D2 receptor mRNA were observed in the lateral striatum of another group of young, middle-aged, and aged rats. Age-related blunting of the NT/N mRNA response to H in the DLSt may be due in part to a decrease in D2 receptors in this structure.",

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note = "Funding Information: Acknowledgements. This work was supported by NARSAD (DJD), by NIA Geriatric Academic Program AG 00503 (DJD), by Scottish Rite Schizophrenia Research Program (KMM, DMD), by the Washington Institute for Mental Illness Research (KMM, DMD), by NIH Grant NS20311 (DMD) and by the Department of Veteran's Affairs (DMD, MWH). We are grateful for the technical assistance of Anne Kalliomaki, Carl Sikkema, and Lori Holden.",

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AU - Dysken, Maurice W.

AU - Dorsa, Daniel M.

N1 - Funding Information: Acknowledgements. This work was supported by NARSAD (DJD), by NIA Geriatric Academic Program AG 00503 (DJD), by Scottish Rite Schizophrenia Research Program (KMM, DMD), by the Washington Institute for Mental Illness Research (KMM, DMD), by NIH Grant NS20311 (DMD) and by the Department of Veteran's Affairs (DMD, MWH). We are grateful for the technical assistance of Anne Kalliomaki, Carl Sikkema, and Lori Holden.

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Blunting of the neurotensin mRNA response to haloperidol in the striatum of aging rats: possible relationship to decline in dopamine D2 receptor expression

Abstract

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Keywords

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