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Chronic infusion of a CRH1 receptor antisense oligodeoxynucleotide into the central nucleus of the amygdala reduced anxiety-related behavior in socially defeated rats
Abstract
We studied the role of central amygdala CRH receptors in behavioral responses to an anxiogenic stimulus. An antisense oligodeoxynucleotide corresponding to the rat CRH1 receptor mRNA was infused chronically into the central amygdaloid nucleus of male rats via osmotic minipumps (0.25 micrograms/0.5 microliters/h). Control groups received infusions of either a scrambled sequence oligodeoxynucleotide or vehicle. On the 4th day of treatment, rats were subjected to 10 min of social defeat and immediately afterwards tested on the elevated plus-maze. Antisense oligodeoxynucleotide-treated rats spent significantly more time exploring the open arms of the plus-maze than scrambled sequence- and vehicle-treated animals, both of which did not differ from each other. The social discrimination test, on the other hand, revealed no difference in juvenile recognition abilities among the treatment groups. Using in situ hybridization and receptor autoradiography, we were not able to detect clear signals of CRH1 receptor mRNA and CRH binding sites in the central amygdaloid nucleus of either group, confirming the reportedly low expression and density of CRH receptors in this brain area. The present data support the view that CRH receptors in the central nucleus of the amygdala are involved in the mediation and expression of anxiety-related behavior, but simultaneously raise questions as to the mechanisms of antisense oligodeoxynucleotide action.
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“Functionally, CEA has been implicated in learning and expression of fear responses,105, 106, 107 as well as the expression of stress-induced anxiety behaviors.108, 109, 110, 111, 112, 113”
From Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress (2014) · cites this paper as [109]
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“…both intracerebroventricular and intra-central nucleus of amygdala infusions of CRF-R1 antisense oligonucleotides antagonized the increase of anxietyrelated behaviour induced by intracerebroventricular injection of CRF or by social defeat, respectively (Liebsch et al., 1995; Skutella et al., 1998).”
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“…social interaction (Campbell et al., 2004) and rat exposure (RET; Tovote et al., 2010) tests, while inhibition by central administration of antisense oligodeoxynucleotides directed against CRF1 mRNA attenuates defensive behavior (Heinrichs et al., 1997; Liebsch et al., 1995; Skutella et al., 1998).”
Suárez, M. M., Rivarola, M. A., Molina, S. M., Levin, G. M., Enders, J., & Paglini, P. A. (2004) · Stress · doi:10.1080/10253890400010705 · Cited by 14
“As described in detail by Liebsch et al. (1995), the apparatus consisted of a plus-shaped platform elevated 50 cm from the floor.”
BackgroundNatriuretic peptides and panic disorder: therapeutic prospects
Kellner, M. B., Jahn, H., & Wiedemann, K. (2003) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.3.3.381 · Cited by 13
Chapter 2. Recent Progress in Corticotropin-Releasing Factor Receptor Agents
McCarthy, J. R., Heinrichs, S. C., & Grigoriadis, D. E. (1999) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(08)60564-3 · Cited by 13
Neuropeptide Regulation of Stress-Induced Behavior
Sztainberg, Y., & Chen, A. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-375097-6.10015-0 · Cited by 12
“Intra-CeA infusions of antisense oligodeoxynucleotides against CRFR1 reduce anxiety-like behavior in socially defeated rats.(97) Intra-BLA administration of astressin B, a CRFR1/2 antagonist, reverses the anxiogenic effects ofUcn1,(98)whereas intra-BLAadministration of the CRFR1-specific antagonist antalarmin prevents…”
BackgroundThe impact of social defeat on basomedial amygdala neuronal activity in adult male rats.
Ritger, A. C., Stickling, C. P., & Ferrara, N. C. (2023) · Behavioural Brain Research · doi:10.1016/j.bbr.2023.114418 · Cited by 11
Byrnes, E. M., Casey, K. M., Carini, L. M., & Bridges, R. S. (2013) · Journal of Neuroendocrinology · doi:10.1111/jne.12113 · Cited by 11
Transgenic Mouse Models: New Tools for Psychiatric Research
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Self-citationChapter 4.1 Peptide receptor ligands to treat anxiety disorders
Steckler, T. (2008) · Handbook of behavioral neuroscience · doi:10.1016/s1569-7339(07)00010-0 · Cited by 10
Ettenberg, A., Cotten, S. W., Brito, M. A., Klein, A. K., Ohana, T. A., Margolin, B. D., Wei, A., & Wenzel, J. M. (2015) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2015.10.002 · Cited by 9
“In contrast, antagonism of CRF function in the CeA or BNST has been reported to attenuate the anxiogenic response to bright light or the stress inherent to the social defeat test (de Jongh et al., 2003; Heinrichs et al., 1992; Liebsch et al., 1995; Swiergiel et al., 1993; Walker et al., 2009) and Erb and Stewart (1999…”
BackgroundRonan, P. J., Korzan, W. J., Johnson, P. L., Lowry, C. A., Renner, K. J., & Summers, C. H. (2023) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2023.1148292 · Cited by 7
“Antagonism of CRF receptors in the CeA or dRN reduces behavioral responses to stressors (Swiergiel et al., 1993; Liebsch et al., 1995; Hammack et al., 2003; Skorzewska et al., 2009), while increasing intra-CeA concentrations of GABA (Skorzewska et al.”
BackgroundTrujillo, V., Masseroni, M. L., Levin, G. M., & Suárez, M. M. (2009) · International Journal of Neuroscience · doi:10.1080/00207450802324713 · Cited by 7
“As described in detail by Liebsch et al. (1995), the apparatus consists of a plus-shaped platform elevated 50 cm from the floor.”
BackgroundCRF antagonists as novel treatment strategies for stress-related disorders
Steckler, T. (2005) · Techniques in the behavioral and neural sciences · doi:10.1016/s0921-0709(05)80065-3 · Cited by 7
Altered emotional behaviors in the diabetes mellitus OLETF type 1 congenic rat
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“As described in detail by Liebsch et al. (1995), the apparatus consisted of a plus-shaped platform elevated 50 cm from the floor.”
BackgroundElgiushy, H. R., Abou-Taleb, N. A., Holz, G. G., Chepurny, O. G., Pirmettis, I. C., Kakabakos, S. E., Karageorgos, V., Liapakis, G., Albohy, A., Abouzid, K. A. M., et al. (2021) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2021.105079 · Cited by 6
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Effects of Corticotropin-Releasing Factor on Circadian Locomotor Rhythm in the Golden Hamster
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Maternal Separation and Lesion of Adtn Alters Anxiety And Adrenal Activity in Male Rats
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“As described in detail by Liebsch et al. (1995), the apparatus consisted of a plusshaped platform elevated 50 cm from the floor.”
BackgroundMolekulare Mechanismen der Depressionstherapie
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“Likewise, subchronic infusion of antisense oligodeoxynucleotides against CRHR1 mRNA in the central nucleus of the amygdala increased open arm duration after resident intruder-induced stress relative to scrambled sequence oligodeoxynucleotide-treated rats and vehicle controls (Liebsch et al., 1995).”
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Mutagenesis and Knockout Models: Hypothalamic-Pituitary-Adrenocortical System
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Mediation of burn-induced hypermetabolism by CRF receptor-2 activity
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Metadata
- Authors
- Liebsch, G., Landgraf, R., Gerstberger, R., Probst, J. C., Wotjak, C. T., Engelmann, M., Holsboer, F., & Montkowski, A.
- Affiliations
- Max Planck Institute of Psychiatry (DE)
- Max Planck Society (DE)
- Corresponding author
- Montkowski, Alexandra
- Venue
- Regulatory Peptides
- Publisher
- Elsevier BV
- Published
- 1995-10
- Volume
- 59
- Issue
- 2
- Pages
- 229-239
- ISSN
- 0167-0115 (ISSN-L)
- OpenAlex
- W1967569415
- Cited by
- 220
- References
- 51
- Citations by year
- 2023: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 4 · 2015: 7 · 2014: 5 · 2013: 10 · 2012: 3
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Regulatory Peptides (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Keywords
- central amygdala, antisense oligodeoxynucleotides, anxiety-like behavior, social defeat, elevated plus maze, social discrimination, gene silencing
- MeSH terms
- Amygdala, Animals, Anxiety, Autoradiography, Base Sequence, Behavior, Animal, Discrimination Learning, Infusions, Parenteral, Functional Laterality, Male, Molecular Sequence Data, Social Behavior, Oligonucleotides, Antisense, Rats, Wistar, In Situ Hybridization, Receptors, Corticotropin-Releasing Hormone, Maze Learning, Rats
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