V1 vasopressin receptor antisense oligodeoxynucleotide into septum reduces vasopressin binding, social discrimination abilities, and anxiety-related behavior in rats
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To develop and validate a vasopressin (AVP) receptor knockdown strategy, we infused an antisense oligodeoxynucleotide to the V1 subtype mRNA into the septum of male rats with osmotic minipumps and measured behavioral, cellular and molecular parameters. Compared to vehicle and scrambled-sequence oligo controls, chronic antisense administration for up to 4 d diminished the ability of the animals to distinguish a previously exposed juvenile from a novel one and to respond to exogenous AVP (1 ng/5 microliters, intracerebroventricular) with an improved social memory. Furthermore, anxiety-related behavior was reduced. As measured in the behaviorally tested rats, antisense treatment resulted in a reduced binding of radiolabeled AVP in the septum, but not in other limbic brain areas (receptor autoradiography), and an increased amount of V1 receptor mRNA (reverse transcriptase PCR), indicating translational arrest and ongoing transcriptional activity. In sense oligo-treated rats, on the other hand, both the social and the anxiety-related behavior scores lay between levels obtained in control and antisense-treated animals. These sense-treated rats showed a slightly reduced V1 receptor density in the septum and reduced receptor mRNA levels, indicating hybridization of the sense oligo to the DNA. The data show the potential of antisense targeting to further reveal relationships between local gene expression, neuropeptide-receptor interactions in distinct brain areas, and behavioral performance.
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AVP typically enhances while OXT reduces anxiety-like behaviors of rats exposed to novel environments.
“Because AVP typically enhances (Landgraf et al., 1995; Beiderbeck et al., 2007) while OXT reduces (Windle et al., 1997; Ring et al., 2006; Blume et al., 2008) anxiety-like behaviors of rats exposed to novel environments”
From Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context (2014) · cites this paper as Landgraf et al., 1995
AVP had a strong anxiogenic effect on elevated plus-maze behavior in juvenile males.
“yet it had a strong anxiogenic effect on elevated plus-maze behavior, confirming previous findings in adult male rats (Landgraf et al., 1995; Beiderbeck et al., 2007; Veenema et al., 2010).”
From Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context (2014) · cites this paper as Landgraf et al., 1995
Chronic intranasal OXT treatment increased V1aR-binding sites in the lateral septum.
“Interestingly, we observed that chronic intranasal OXT treatment increased the V1aR-binding sites in the lateral septum, that is, þ 18% in OXT 0.15 IU-treated mice and þ 31% in OXT 0.3 IU-treated mice (Figure 3b).”
From Chronic and acute intranasal oxytocin produce divergent social effects in mice (2014) · cites this paper as Landgraf et al, 1995
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CALDWELL, H., WERSINGER, S., & YOUNGIII, W. (2008) · Progress in Brain Research · doi:10.1016/s0079-6123(08)00406-8 · Cited by 64 · see citing works
Rigney, N., Whylings, J., Mieda, M., de Vries, G. J., & Petrulis, A. (2019) · eNeuro · doi:10.1523/eneuro.0415-18.2019 · Cited by 63 · see citing works
“For example, injections of AVP or V1aR antagonists, or V1aR knockdown within LS all support the idea that AVP is anxiogenic at this site (Landgraf et al., 1995; Liebsch et al., 1996; Beiderbeck et al., 2007).”
ResultKompier, N. F., Keysers, C., Gazzola, V., Lucassen, P. J., & Krugers, H. J. (2019) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2019.00143 · Cited by 53 · see citing works
Song, Z., Larkin, T. E., Malley, M. O., & Albers, H. E. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2016.02.004 · Cited by 47 · see citing works
Septal oxytocin administration impairs peer affiliation via V1a receptors in female meadow voles
Anacker, A. M. J., Christensen, J. D., LaFlamme, E. M., Grunberg, D. M., & Beery, A. K. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.02.025 · Cited by 44 · see citing works
Rigney, N., Zbib, A., de Vries, G. J., & Petrulis, A. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13083 · Cited by 29 · see citing works
McEwen (2004) · doi:10.1016/s1054-3589(04)50016-9 · Cited by 22 · see citing works
- Authors
- Landgraf, R., Gerstberger, R., Montkowski, A., Probst, J., Wotjak, C., Holsboer, F., & Engelmann, M.
- Affiliations
- Max Planck Institute of Psychiatry (DE)
- Max Planck Society (DE)
- ORCID
- Engelmann, M
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1995-06-01
- Volume
- 15
- Issue
- 6
- Pages
- 4250-4258
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6577715
- OpenAlex
- W1623788409
- Cited by
- 341
- References
- 52
- Citations by year
- 2025: 4 · 2024: 5 · 2023: 3 · 2022: 7 · 2021: 11 · 2020: 3 · 2019: 9 · 2018: 12 · 2017: 8 · 2016: 11 · 2015: 6 · 2014: 14 · 2013: 11 · 2012: 7
- FWCI
- 29.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- V1 vasopressin receptor, antisense oligodeoxynucleotides, gene knockdown, septum, social discrimination, social memory, anxiety-like behavior, limbic system, translational arrest
- MeSH terms
- Analysis of Variance, Animals, Anxiety, Arginine Vasopressin, Base Sequence, Brain, Discrimination, Psychological, Infusions, Parenteral, Male, Molecular Sequence Data, RNA, Messenger, Social Behavior, Time Factors, Polymerase Chain Reaction, Oligonucleotides, Antisense, Rats, Wistar, Receptors, Vasopressin, Rats
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