Chlordiazepoxide-induced expression of c-Fos in the central extended amygdala and other brain regions of the C57BL/6J and DBA/2J inbred mouse strains: Relationships to mechanisms of ethanol action

Barbara Hitzemann, Robert Hitzemann

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: Previous studies have established an association between the ethanol-induced locomotor response and activation of the central nucleus of the amygdala (CeA) as determined by changes in the number of Fos-like immunoreactive (Fos-li) neurons. The purpose of the current study was to determine if the benzodiazepine chlordiazepoxide (CDP) would produce similar effects to ethanol on behavior and the CeA. Methods: In experiment 1, C57BL/6J (B6) and DBA/2J (D2) mice were administered CDP over a dose range of 3 to 30 mg/kg and the effects on locomotor behavior and the number of Fos-li neurons in the extended CeA determined. For experiment 2, B6D2 F2 intercross animals were phenotyped for their locomotor response to ethanol using a test- retest design. The activity responsive and nonresponsive extreme phenotypes were then tested in the same fashion as the inbred strains. Results: Similar to ethanol, CDP increased locomotor activity in the D2 strain but not the B6 strain; furthermore, the D2 strain was 3 to 10 times more sensitive than the B6 strain in terms of CDP activating the CeA and the associated lateral posterior aspect of the bed nucleus of the stria terminalis (BSTLP). In the shell of the nucleus accumbens (NAc), CDP inhibited the number of Fos- positive neurons in both strains. CDP also discriminated between the responsive and nonresponsive extremes both in terms of behavior and activation of the CeA. Conclusions: Overall, these data point to the importance of GABA(A) mediated mechanisms in the ethanol-induced locomotor response. It is suggested that both drugs block the feed-forward inhibition in the CeA, resulting in activation of the GABAergic projection neurons. The overall net effect of CDP or ethanol administration on the output from the CeA will be inhibitory, from which it follows that the locomotor activation response must be associated with the selective inhibition of some behavior or ensembles of behaviors that are known to be mediated by the CeA and reduce locomotor activity (i.e., the 'freezing' response).

Original languageEnglish (US)
Pages (from-to)1158-1172
Number of pages15
JournalAlcoholism: Clinical and Experimental Research
Volume23
Issue number7
StatePublished - Jul 1999
Externally publishedYes

Fingerprint

Chlordiazepoxide
Inbred Strains Mice
Brain
Ethanol
Neurons
Chemical activation
Locomotion
GABAergic Neurons
Septal Nuclei
Inbred DBA Mouse
Central Amygdaloid Nucleus
Benzodiazepines
Freezing
Nucleus Accumbens
gamma-Aminobutyric Acid
Animals
Experiments
Association reactions
Phenotype
Pharmaceutical Preparations

Keywords

  • c-Fos
  • Central Nucleus
  • Chlordiazepoxide
  • Ethanol
  • Locomotion

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

@article{dce6d2534ad1426caa5fd47528a3523d,
title = "Chlordiazepoxide-induced expression of c-Fos in the central extended amygdala and other brain regions of the C57BL/6J and DBA/2J inbred mouse strains: Relationships to mechanisms of ethanol action",
abstract = "Background: Previous studies have established an association between the ethanol-induced locomotor response and activation of the central nucleus of the amygdala (CeA) as determined by changes in the number of Fos-like immunoreactive (Fos-li) neurons. The purpose of the current study was to determine if the benzodiazepine chlordiazepoxide (CDP) would produce similar effects to ethanol on behavior and the CeA. Methods: In experiment 1, C57BL/6J (B6) and DBA/2J (D2) mice were administered CDP over a dose range of 3 to 30 mg/kg and the effects on locomotor behavior and the number of Fos-li neurons in the extended CeA determined. For experiment 2, B6D2 F2 intercross animals were phenotyped for their locomotor response to ethanol using a test- retest design. The activity responsive and nonresponsive extreme phenotypes were then tested in the same fashion as the inbred strains. Results: Similar to ethanol, CDP increased locomotor activity in the D2 strain but not the B6 strain; furthermore, the D2 strain was 3 to 10 times more sensitive than the B6 strain in terms of CDP activating the CeA and the associated lateral posterior aspect of the bed nucleus of the stria terminalis (BSTLP). In the shell of the nucleus accumbens (NAc), CDP inhibited the number of Fos- positive neurons in both strains. CDP also discriminated between the responsive and nonresponsive extremes both in terms of behavior and activation of the CeA. Conclusions: Overall, these data point to the importance of GABA(A) mediated mechanisms in the ethanol-induced locomotor response. It is suggested that both drugs block the feed-forward inhibition in the CeA, resulting in activation of the GABAergic projection neurons. The overall net effect of CDP or ethanol administration on the output from the CeA will be inhibitory, from which it follows that the locomotor activation response must be associated with the selective inhibition of some behavior or ensembles of behaviors that are known to be mediated by the CeA and reduce locomotor activity (i.e., the 'freezing' response).",
keywords = "c-Fos, Central Nucleus, Chlordiazepoxide, Ethanol, Locomotion",
author = "Barbara Hitzemann and Robert Hitzemann",
year = "1999",
month = "7",
language = "English (US)",
volume = "23",
pages = "1158--1172",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
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TY - JOUR

T1 - Chlordiazepoxide-induced expression of c-Fos in the central extended amygdala and other brain regions of the C57BL/6J and DBA/2J inbred mouse strains

T2 - Relationships to mechanisms of ethanol action

AU - Hitzemann, Barbara

AU - Hitzemann, Robert

PY - 1999/7

Y1 - 1999/7

N2 - Background: Previous studies have established an association between the ethanol-induced locomotor response and activation of the central nucleus of the amygdala (CeA) as determined by changes in the number of Fos-like immunoreactive (Fos-li) neurons. The purpose of the current study was to determine if the benzodiazepine chlordiazepoxide (CDP) would produce similar effects to ethanol on behavior and the CeA. Methods: In experiment 1, C57BL/6J (B6) and DBA/2J (D2) mice were administered CDP over a dose range of 3 to 30 mg/kg and the effects on locomotor behavior and the number of Fos-li neurons in the extended CeA determined. For experiment 2, B6D2 F2 intercross animals were phenotyped for their locomotor response to ethanol using a test- retest design. The activity responsive and nonresponsive extreme phenotypes were then tested in the same fashion as the inbred strains. Results: Similar to ethanol, CDP increased locomotor activity in the D2 strain but not the B6 strain; furthermore, the D2 strain was 3 to 10 times more sensitive than the B6 strain in terms of CDP activating the CeA and the associated lateral posterior aspect of the bed nucleus of the stria terminalis (BSTLP). In the shell of the nucleus accumbens (NAc), CDP inhibited the number of Fos- positive neurons in both strains. CDP also discriminated between the responsive and nonresponsive extremes both in terms of behavior and activation of the CeA. Conclusions: Overall, these data point to the importance of GABA(A) mediated mechanisms in the ethanol-induced locomotor response. It is suggested that both drugs block the feed-forward inhibition in the CeA, resulting in activation of the GABAergic projection neurons. The overall net effect of CDP or ethanol administration on the output from the CeA will be inhibitory, from which it follows that the locomotor activation response must be associated with the selective inhibition of some behavior or ensembles of behaviors that are known to be mediated by the CeA and reduce locomotor activity (i.e., the 'freezing' response).

AB - Background: Previous studies have established an association between the ethanol-induced locomotor response and activation of the central nucleus of the amygdala (CeA) as determined by changes in the number of Fos-like immunoreactive (Fos-li) neurons. The purpose of the current study was to determine if the benzodiazepine chlordiazepoxide (CDP) would produce similar effects to ethanol on behavior and the CeA. Methods: In experiment 1, C57BL/6J (B6) and DBA/2J (D2) mice were administered CDP over a dose range of 3 to 30 mg/kg and the effects on locomotor behavior and the number of Fos-li neurons in the extended CeA determined. For experiment 2, B6D2 F2 intercross animals were phenotyped for their locomotor response to ethanol using a test- retest design. The activity responsive and nonresponsive extreme phenotypes were then tested in the same fashion as the inbred strains. Results: Similar to ethanol, CDP increased locomotor activity in the D2 strain but not the B6 strain; furthermore, the D2 strain was 3 to 10 times more sensitive than the B6 strain in terms of CDP activating the CeA and the associated lateral posterior aspect of the bed nucleus of the stria terminalis (BSTLP). In the shell of the nucleus accumbens (NAc), CDP inhibited the number of Fos- positive neurons in both strains. CDP also discriminated between the responsive and nonresponsive extremes both in terms of behavior and activation of the CeA. Conclusions: Overall, these data point to the importance of GABA(A) mediated mechanisms in the ethanol-induced locomotor response. It is suggested that both drugs block the feed-forward inhibition in the CeA, resulting in activation of the GABAergic projection neurons. The overall net effect of CDP or ethanol administration on the output from the CeA will be inhibitory, from which it follows that the locomotor activation response must be associated with the selective inhibition of some behavior or ensembles of behaviors that are known to be mediated by the CeA and reduce locomotor activity (i.e., the 'freezing' response).

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KW - Central Nucleus

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KW - Ethanol

KW - Locomotion

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