Sexually Dimorphic Behavioral Profile in a Transgenic Model Enabling Targeted Recombination in Active Neurons in Response to Ketamine and (2R,6R)-Hydroxynorketamine Administration
Abstract
:1. Introduction
2. Results
2.1. Behavioral Characterization
2.1.1. Ketamine and (2R,6R)-HNK Do not Affect Spatial (Working) or Episodic Memory
2.1.2. Sex, but Not Treatment, Affected Social Behavior and Anxiety
2.1.3. Sex Influenced the Antidepressant-Like Effects of Ketamine and (2R,6R)-HNK in the Forced Swim Test (FST)
2.2. Molecular Characterization
2.2.1. Activated Nuclei Upon Ketamine and (2R,6R)-HNK Administration
2.2.2. Ketamine Increase BDNF Intensity in DG and CA3
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Compounds
4.3. Behavioral Procedure
4.3.1. Behavioral Battery
4.3.2. Forced Swim Test (FST)
4.4. Tissue Collection
4.5. Immunohistochemistry
4.6. In Situ Hybridization
4.6.1. Bdnf RNA Probe Synthesis
4.6.2. Digoxigenin (DIG) Labelling
4.6.3. In Situ Hybridization
4.7. Microscopy
4.8. Intensity Quantification
4.9. Statistical Analysis
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Appendix A
References
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Behavioural Test | Effect | p Value | F | dfn, dfd |
---|---|---|---|---|
Spontaneous alternations | Treatment | 0.7364 | 0.3077 | 2, 56 |
Sex | 0.8434 | 0.0394 | 1, 56 | |
Interaction | 0.0816 | 2.621 | 2, 56 | |
SORT | Treatment | 0.7892 | 0.2377 | 2, 54 |
Sex | 0.0678 | 3.475 | 1, 54 | |
Interaction | 0.5034 | 0.6952 | 2, 54 | |
NORT | Treatment | 0.6674 | 0.4085 | 2, 40 |
Sex | 0.1274 | 2.423 | 1, 40 | |
Interaction | 0.4187 | 0.8899 | 2, 40 | |
OF | Treatment | 0.8226 | 0.196 | 2, 55 |
Sex | 0.5454 | 0.3703 | 1, 55 | |
Interaction | 0.4192 | 0.8833 | 2, 55 | |
Sociability | Treatment | 0.1729 | 1.816 | 2, 52 |
Sex | 0.0133 * | 6.574 | 1, 52 | |
Interaction | 0.8376 | 0.1779 | 2, 52 | |
LD box | Treatment | 0.1593 | 1.9 | 2, 55 |
Sex | 0.0403 * | 4.411 | 1, 55 | |
Interaction | 0.6075 | 0.503 | 2, 55 |
Behavioural Test | Treatment | Male | Female | ||||
---|---|---|---|---|---|---|---|
p Value | t | df | p Value | t | df | ||
SORT | Saline | 0.694 | 0.417 | 5 | 0.0003 | 4.851 | 13 |
Ketamine | 0.2043 | 1.424 | 6 | 0.0029 | 3.65 | 13 | |
HNK | 0.5703 | 0.5954 | 7 | 0.0034 | 3.717 | 11 | |
NORT | Saline | 0.0817 | 2.581 | 3 | 0.0412 | 2.311 | 11 |
Ketamine | 0.216 | 1.468 | 4 | 0.5445 | 0.6274 | 10 | |
HNK | 0.149 | 1.655 | 6 | 0.1432 | 1.649 | 7 | |
Sociability | Saline | 0.0016 | 6.228 | 5 | <0.0001 | 8.531 | 12 |
Ketamine | 0.0001 | 8.657 | 6 | <0.0001 | 11.96 | 12 | |
HNK | <0.0001 | 13.02 | 7 | <0.0001 | 9.878 | 11 | |
Bedding Preference | Saline | 0.0952 | 1.978 | 6 | 0.1845 | 1.402 | 13 |
Ketamine | 0.0339 | 2.736 | 6 | 0.2512 | 1.201 | 13 | |
HNK | <0.0001 | 11.4 | 7 | 0.3102 | 1.064 | 11 |
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Herzog, D.P.; Mellema, R.M.; Remmers, F.; Lutz, B.; Müller, M.B.; Treccani, G. Sexually Dimorphic Behavioral Profile in a Transgenic Model Enabling Targeted Recombination in Active Neurons in Response to Ketamine and (2R,6R)-Hydroxynorketamine Administration. Int. J. Mol. Sci. 2020, 21, 2142. https://doi.org/10.3390/ijms21062142
Herzog DP, Mellema RM, Remmers F, Lutz B, Müller MB, Treccani G. Sexually Dimorphic Behavioral Profile in a Transgenic Model Enabling Targeted Recombination in Active Neurons in Response to Ketamine and (2R,6R)-Hydroxynorketamine Administration. International Journal of Molecular Sciences. 2020; 21(6):2142. https://doi.org/10.3390/ijms21062142
Chicago/Turabian StyleHerzog, David P., Ratnadevi M. Mellema, Floortje Remmers, Beat Lutz, Marianne B. Müller, and Giulia Treccani. 2020. "Sexually Dimorphic Behavioral Profile in a Transgenic Model Enabling Targeted Recombination in Active Neurons in Response to Ketamine and (2R,6R)-Hydroxynorketamine Administration" International Journal of Molecular Sciences 21, no. 6: 2142. https://doi.org/10.3390/ijms21062142