Substantia nigra pars reticulata is crucially involved in barbiturate and ethanol withdrawal in mice

Gang Chen, Laura B. Kozell, Kari Buck

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Sedative-hypnotic CNS depressant drugs are widely prescribed to treat a variety of disorders, and are abused for their sedative and euphoric effects. Physiological dependence and associated withdrawal episodes are thought to constitute a motivational force that sustains their use/abuse and may contribute to relapse in dependent individuals. Although no animal model duplicates depressant dependence, models for specific factors, like withdrawal, are useful for identifying potential neural determinants of liability in humans. Recent analyses implicate the caudolateral substantia nigra pars reticulata (clSNr) in withdrawal following acute and repeated ethanol exposures in mice, but did not assess its impact on withdrawal from other sedative-hypnotics or whether intrinsic neurons or fibers of passage are involved. Here, we demonstrate that bilateral chemical (ibotenic acid) lesions of the clSNr attenuate barbiturate (pentobarbital) and ethanol withdrawal. Chemical lesions did not affect convulsions in response to pentylenetetrazole, which blocks GABAA receptor-mediated transmission. Our results demonstrate that the clSNr nucleus itself rather than fibers of passage is crucial to its effects on barbiturate and ethanol withdrawal. These findings support suggest that clSNr could be one of the shared neural substrates mediating withdrawal from sedative-hypnotic drugs.

Original languageEnglish (US)
Pages (from-to)152-157
Number of pages6
JournalBehavioural Brain Research
Volume218
Issue number1
DOIs
StatePublished - Mar 17 2011

Fingerprint

Hypnotics and Sedatives
Ethanol
Central Nervous System Depressants
Ibotenic Acid
Pentylenetetrazole
Pentobarbital
GABA-A Receptors
Pharmaceutical Preparations
Seizures
Animal Models
Neurons
Recurrence
Pars Reticulata
barbituric acid

Keywords

  • Convulsion
  • Ibotenic acid
  • Lesion
  • Sedative-hypnotic
  • Seizure

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Substantia nigra pars reticulata is crucially involved in barbiturate and ethanol withdrawal in mice. / Chen, Gang; Kozell, Laura B.; Buck, Kari.

In: Behavioural Brain Research, Vol. 218, No. 1, 17.03.2011, p. 152-157.

Research output: Contribution to journalArticle

@article{33febbfbcf2b44939db8d9897791c93e,
title = "Substantia nigra pars reticulata is crucially involved in barbiturate and ethanol withdrawal in mice",
abstract = "Sedative-hypnotic CNS depressant drugs are widely prescribed to treat a variety of disorders, and are abused for their sedative and euphoric effects. Physiological dependence and associated withdrawal episodes are thought to constitute a motivational force that sustains their use/abuse and may contribute to relapse in dependent individuals. Although no animal model duplicates depressant dependence, models for specific factors, like withdrawal, are useful for identifying potential neural determinants of liability in humans. Recent analyses implicate the caudolateral substantia nigra pars reticulata (clSNr) in withdrawal following acute and repeated ethanol exposures in mice, but did not assess its impact on withdrawal from other sedative-hypnotics or whether intrinsic neurons or fibers of passage are involved. Here, we demonstrate that bilateral chemical (ibotenic acid) lesions of the clSNr attenuate barbiturate (pentobarbital) and ethanol withdrawal. Chemical lesions did not affect convulsions in response to pentylenetetrazole, which blocks GABAA receptor-mediated transmission. Our results demonstrate that the clSNr nucleus itself rather than fibers of passage is crucial to its effects on barbiturate and ethanol withdrawal. These findings support suggest that clSNr could be one of the shared neural substrates mediating withdrawal from sedative-hypnotic drugs.",
keywords = "Convulsion, Ibotenic acid, Lesion, Sedative-hypnotic, Seizure",
author = "Gang Chen and Kozell, {Laura B.} and Kari Buck",
year = "2011",
month = "3",
day = "17",
doi = "10.1016/j.bbr.2010.10.025",
language = "English (US)",
volume = "218",
pages = "152--157",
journal = "Behavioural Brain Research",
issn = "0166-4328",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Substantia nigra pars reticulata is crucially involved in barbiturate and ethanol withdrawal in mice

AU - Chen, Gang

AU - Kozell, Laura B.

AU - Buck, Kari

PY - 2011/3/17

Y1 - 2011/3/17

N2 - Sedative-hypnotic CNS depressant drugs are widely prescribed to treat a variety of disorders, and are abused for their sedative and euphoric effects. Physiological dependence and associated withdrawal episodes are thought to constitute a motivational force that sustains their use/abuse and may contribute to relapse in dependent individuals. Although no animal model duplicates depressant dependence, models for specific factors, like withdrawal, are useful for identifying potential neural determinants of liability in humans. Recent analyses implicate the caudolateral substantia nigra pars reticulata (clSNr) in withdrawal following acute and repeated ethanol exposures in mice, but did not assess its impact on withdrawal from other sedative-hypnotics or whether intrinsic neurons or fibers of passage are involved. Here, we demonstrate that bilateral chemical (ibotenic acid) lesions of the clSNr attenuate barbiturate (pentobarbital) and ethanol withdrawal. Chemical lesions did not affect convulsions in response to pentylenetetrazole, which blocks GABAA receptor-mediated transmission. Our results demonstrate that the clSNr nucleus itself rather than fibers of passage is crucial to its effects on barbiturate and ethanol withdrawal. These findings support suggest that clSNr could be one of the shared neural substrates mediating withdrawal from sedative-hypnotic drugs.

AB - Sedative-hypnotic CNS depressant drugs are widely prescribed to treat a variety of disorders, and are abused for their sedative and euphoric effects. Physiological dependence and associated withdrawal episodes are thought to constitute a motivational force that sustains their use/abuse and may contribute to relapse in dependent individuals. Although no animal model duplicates depressant dependence, models for specific factors, like withdrawal, are useful for identifying potential neural determinants of liability in humans. Recent analyses implicate the caudolateral substantia nigra pars reticulata (clSNr) in withdrawal following acute and repeated ethanol exposures in mice, but did not assess its impact on withdrawal from other sedative-hypnotics or whether intrinsic neurons or fibers of passage are involved. Here, we demonstrate that bilateral chemical (ibotenic acid) lesions of the clSNr attenuate barbiturate (pentobarbital) and ethanol withdrawal. Chemical lesions did not affect convulsions in response to pentylenetetrazole, which blocks GABAA receptor-mediated transmission. Our results demonstrate that the clSNr nucleus itself rather than fibers of passage is crucial to its effects on barbiturate and ethanol withdrawal. These findings support suggest that clSNr could be one of the shared neural substrates mediating withdrawal from sedative-hypnotic drugs.

KW - Convulsion

KW - Ibotenic acid

KW - Lesion

KW - Sedative-hypnotic

KW - Seizure

UR - http://www.scopus.com/inward/record.url?scp=78650164438&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650164438&partnerID=8YFLogxK

U2 - 10.1016/j.bbr.2010.10.025

DO - 10.1016/j.bbr.2010.10.025

M3 - Article

C2 - 20974184

AN - SCOPUS:78650164438

VL - 218

SP - 152

EP - 157

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

IS - 1

ER -