Overlapping and Distinct Brain Regions Associated with the Anxiolytic Effects of Chlordiazepoxide and Chronic Fluoxetine
Open accessAbstract
Little is known about the sites of action for the behavioral effects of chronic antidepressants. The novelty-induced hypophagia (NIH) test is one of few animal behavioral tests sensitive to acute benzodiazepines and chronic antidepressants. The goals of these experiments were to examine patterns of brain activation associated with the behavioral response to novelty and identify regions that could regulate the anxiolytic effects of acute benzodiazepine and chronic antidepressant treatments, measured using the NIH test. In the first experiment, rats were treated acutely with the anxiolytic, chlordiazepoxide (2.5 or 5 mg/kg, i.p.). In separate experiments, animals were implanted with osmotic minipumps delivering vehicle or fluoxetine (5 or 20 mg/kg per day s.c.) for 3 or 28 days. NIH was assessed by giving animals access to a familiar palatable food in a novel environment. Associated brain areas were identified using c-fos immunohistochemistry. NIH was mitigated by acute chlordiazepoxide and chronic fluoxetine. Both drugs reversed novelty-induced changes in c-fos expression in the lateral division of the posterolateral part of the bed nucleus of the stria terminalis (STLP), cingulate cortex (Cg), and dorsal field CA2 of the hippocampus (dCA2). Chronic fluoxetine additionally increased c-fos expression in the anterior nucleus accumbens (aAcb) and the piriform cortex (Pir). The effects of the drugs on c-fos expression in many regions correlated with anxiolytic efficacy. These findings identified brain regions where the effects of chronic antidepressants and benzodiazepines may converge to produce anxiolytic activity, as well as distinct sites of action for the two classes of drugs.
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Both acute chlordiazepoxide and chronic fluoxetine decreased stress-induced c-Fos increases in the lateral bed nucleus of the stria terminalis, providing some of the first evidence that the potential anxiolytic effects of both compounds may be mediated by actions in the bed nucleus of the stria terminalis.
“both acute chlordiazepoxide and chronic fluoxetine decreased stress-induced c-Fos increases in the BNSTL, providing some of the first evidence that the potential anxiolytic effects of both compounds may be mediated by actions in the BNST (Bechtholt et al, 2008).”
From Phasic vs Sustained Fear in Rats and Humans: Role of the Extended Amygdala in Fear vs Anxiety (2010) · cites this paper as Bechtholt et al, 2008
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Experimental — accuracy not yet measuredLong-term fluoxetine lowers the stress-induced rise in c-Fos within the BNSTL.
“chronic fluoxetine decreased stress-induced c-Fos increases in the BNSTL (Bechtholt et al, 2008).”
From Phasic vs Sustained Fear in Rats and Humans: Role of the Extended Amygdala in Fear vs Anxiety (2010) · cites this paper as Bechtholt et al, 2008
The c-Fos Expression Associated with NIH section says novelty tended to decrease c-Fos in the lateral posterolateral bed nucleus of the stria terminalis (STLP), and chronic fluoxetine reversed that change. The Discussion says fluoxetine normalized novelty-inhibited c-Fos in the STLP—the opposite of decreasing a stress-induced rise. Page numbers are unavailable in our copy. (LLM, conf=0.90)
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- Authors
- Bechtholt, A. J., Valentino, R. J., & Lucki, I.
- Affiliations
- University of Pennsylvania (US)
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Lucki, Irwin
- Venue
- Neuropsychopharmacology
- Published
- 2007-11-07
- Volume
- 33
- Issue
- 9
- Pages
- 2117-2130
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2072640218
- Cited by
- 40
- References
- 46
- Citations by year
- 2025: 2 · 2024: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 6 · 2012: 2
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health
- National Institute of Mental Health (MH 40008, T32MH014654, MH072832, U01MH072832)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- chlordiazepoxide, fluoxetine, anxiolytic effects, novelty-induced hypophagia, Fos expression, site of action, benzodiazepines, bed nucleus of the stria terminalis, cingulate cortex, hippocampal CA2, piriform cortex
- MeSH terms
- Analysis of Variance, Animals, Behavior, Animal, Brain, Brain Mapping, Chlordiazepoxide, Dose-Response Relationship, Drug, Drug Administration Schedule, Feeding Behavior, Fluoxetine, Gene Expression Regulation, Male, Anti-Anxiety Agents, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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