Elevated startle during withdrawal from acute morphine: A model of opiate withdrawal and anxiety

Andrew C. Harris; Jonathan C. Gewirtz

doi:10.1007/s00213-003-1573-0

Elevated startle during withdrawal from acute morphine: A model of opiate withdrawal and anxiety

Andrew C. Harris, Jonathan C. Gewirtz

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

64 Scopus citations

Abstract

Rationale: An elevated startle response has been observed in humans and animals during withdrawal from multiple substances of abuse, a phenomenon thought to reflect the anxiogenic effects of withdrawal. Although anxiety is a common symptom of opiate withdrawal, few studies have examined the effects of morphine withdrawal on acoustic startle. Objective: To develop a procedure for assessing opiate dependence through measurement of the startle reflex in rats. Methods: The effects of opiate withdrawal on startle were evaluated using both spontaneous and naloxone-precipitated withdrawal from an acute dose of morphine. The ability of the treatment drugs clonidine and chlordiazepoxide to block withdrawal-induced increases in startle was also tested. Results: Spontaneous withdrawal from an injection of morphine sulfate produced a significant increase in acoustic startle 2 h (3.2 mg/kg) or 4 h (10 mg/kg) after drug administration. Morphine withdrawal (10 mg/kg morphine sulfate) precipitated by the opiate antagonist naloxone (2.5 mg/kg) also produced a significant increase in startle magnitude. This elevation of startle was blocked by both clonidine (35 μg/kg) and chlordiazepoxide (10 mg/kg). Conclusions: These data demonstrate that both spontaneous and precipitated withdrawal from an acutely administered opiate produce anxiety-like effects on acoustic startle. This paradigm may be useful in the study of anxiety and the early mechanisms of drug dependence.

Original language	English (US)
Pages (from-to)	140-147
Number of pages	8
Journal	Psychopharmacology
Volume	171
Issue number	2
DOIs	https://doi.org/10.1007/s00213-003-1573-0
State	Published - Jan 2004

Bibliographical note

Funding Information:
Acknowledgements The authors wish to thank David Atkinson, Stephanie Hanes, and Michelle Pilat and for their assistance in conducting the experiments. In addition, we thank Drs. Lisa Schrott, Monica Luciana, and Megan Gunnar of the University of Minnesota for helpful discussion of the manuscript. This work was supported by the National Institute on Drug Abuse T32 DA07097 and the University of Minnesota.

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

Keywords

Anxiety
Benzodiazepine
Clonidine
Morphine
Startle
Withdrawal

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Elevated startle during withdrawal from acute morphine: A model of opiate withdrawal and anxiety",

abstract = "Rationale: An elevated startle response has been observed in humans and animals during withdrawal from multiple substances of abuse, a phenomenon thought to reflect the anxiogenic effects of withdrawal. Although anxiety is a common symptom of opiate withdrawal, few studies have examined the effects of morphine withdrawal on acoustic startle. Objective: To develop a procedure for assessing opiate dependence through measurement of the startle reflex in rats. Methods: The effects of opiate withdrawal on startle were evaluated using both spontaneous and naloxone-precipitated withdrawal from an acute dose of morphine. The ability of the treatment drugs clonidine and chlordiazepoxide to block withdrawal-induced increases in startle was also tested. Results: Spontaneous withdrawal from an injection of morphine sulfate produced a significant increase in acoustic startle 2 h (3.2 mg/kg) or 4 h (10 mg/kg) after drug administration. Morphine withdrawal (10 mg/kg morphine sulfate) precipitated by the opiate antagonist naloxone (2.5 mg/kg) also produced a significant increase in startle magnitude. This elevation of startle was blocked by both clonidine (35 μg/kg) and chlordiazepoxide (10 mg/kg). Conclusions: These data demonstrate that both spontaneous and precipitated withdrawal from an acutely administered opiate produce anxiety-like effects on acoustic startle. This paradigm may be useful in the study of anxiety and the early mechanisms of drug dependence.",

keywords = "Anxiety, Benzodiazepine, Clonidine, Morphine, Startle, Withdrawal",

author = "Harris, {Andrew C.} and Gewirtz, {Jonathan C.}",

note = "Funding Information: Acknowledgements The authors wish to thank David Atkinson, Stephanie Hanes, and Michelle Pilat and for their assistance in conducting the experiments. In addition, we thank Drs. Lisa Schrott, Monica Luciana, and Megan Gunnar of the University of Minnesota for helpful discussion of the manuscript. This work was supported by the National Institute on Drug Abuse T32 DA07097 and the University of Minnesota. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.",

year = "2004",

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doi = "10.1007/s00213-003-1573-0",

language = "English (US)",

volume = "171",

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AU - Gewirtz, Jonathan C.

N1 - Funding Information: Acknowledgements The authors wish to thank David Atkinson, Stephanie Hanes, and Michelle Pilat and for their assistance in conducting the experiments. In addition, we thank Drs. Lisa Schrott, Monica Luciana, and Megan Gunnar of the University of Minnesota for helpful discussion of the manuscript. This work was supported by the National Institute on Drug Abuse T32 DA07097 and the University of Minnesota. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.

PY - 2004/1

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N2 - Rationale: An elevated startle response has been observed in humans and animals during withdrawal from multiple substances of abuse, a phenomenon thought to reflect the anxiogenic effects of withdrawal. Although anxiety is a common symptom of opiate withdrawal, few studies have examined the effects of morphine withdrawal on acoustic startle. Objective: To develop a procedure for assessing opiate dependence through measurement of the startle reflex in rats. Methods: The effects of opiate withdrawal on startle were evaluated using both spontaneous and naloxone-precipitated withdrawal from an acute dose of morphine. The ability of the treatment drugs clonidine and chlordiazepoxide to block withdrawal-induced increases in startle was also tested. Results: Spontaneous withdrawal from an injection of morphine sulfate produced a significant increase in acoustic startle 2 h (3.2 mg/kg) or 4 h (10 mg/kg) after drug administration. Morphine withdrawal (10 mg/kg morphine sulfate) precipitated by the opiate antagonist naloxone (2.5 mg/kg) also produced a significant increase in startle magnitude. This elevation of startle was blocked by both clonidine (35 μg/kg) and chlordiazepoxide (10 mg/kg). Conclusions: These data demonstrate that both spontaneous and precipitated withdrawal from an acutely administered opiate produce anxiety-like effects on acoustic startle. This paradigm may be useful in the study of anxiety and the early mechanisms of drug dependence.

AB - Rationale: An elevated startle response has been observed in humans and animals during withdrawal from multiple substances of abuse, a phenomenon thought to reflect the anxiogenic effects of withdrawal. Although anxiety is a common symptom of opiate withdrawal, few studies have examined the effects of morphine withdrawal on acoustic startle. Objective: To develop a procedure for assessing opiate dependence through measurement of the startle reflex in rats. Methods: The effects of opiate withdrawal on startle were evaluated using both spontaneous and naloxone-precipitated withdrawal from an acute dose of morphine. The ability of the treatment drugs clonidine and chlordiazepoxide to block withdrawal-induced increases in startle was also tested. Results: Spontaneous withdrawal from an injection of morphine sulfate produced a significant increase in acoustic startle 2 h (3.2 mg/kg) or 4 h (10 mg/kg) after drug administration. Morphine withdrawal (10 mg/kg morphine sulfate) precipitated by the opiate antagonist naloxone (2.5 mg/kg) also produced a significant increase in startle magnitude. This elevation of startle was blocked by both clonidine (35 μg/kg) and chlordiazepoxide (10 mg/kg). Conclusions: These data demonstrate that both spontaneous and precipitated withdrawal from an acutely administered opiate produce anxiety-like effects on acoustic startle. This paradigm may be useful in the study of anxiety and the early mechanisms of drug dependence.

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KW - Morphine

KW - Startle

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Elevated startle during withdrawal from acute morphine: A model of opiate withdrawal and anxiety

Abstract

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Keywords

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