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Induction of aberrant agonistic behavior by a combination of serotonergic and dopaminergic manipulation in rats

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Abstract

Serotonin (5-HT) and dopamine (DA) are involved in the regulation of social behaviors. However, the effects of their interactions on social behavior are not well understood. In this study, rats received a serotonergic neurotoxin injection into the raphe nuclei and/or systemic administration of l-3, 4-dihydroxyphenylalanine (l-DOPA), and their agonistic behaviors were investigated using the resident–intruder (RI) paradigm. Rats in the DA + /5-HT-group, which were administered both monoaminergic treatments, exhibited intense jump and flight responses to intruders. These behaviors were not observed in rats that received either 5-HT lesions or l-DOPA treatment only. To address the neural basis of these aberrant behaviors, we compared c-Fos immunoreactivity in the brain among the different groups. The DA + /5-HT-group had c-Fos activation in areas related to anti-predatory defensive behaviors, such as the ventromedial hypothalamic nucleus, premammillary nucleus, and periaqueductal gray. Moreover, this group had increased c-Fos expression in the ventroposterior part of the anterior olfactory nucleus (AOVP). To test the involvement of this area in the aberrant behaviors, cytotoxic lesions were performed in the AOVP prior to the monoaminergic treatments, and subsequent behaviors were examined using the RI test. The AOVP-lesioned DA + /5-HT-rats had attenuation of the aberrant behaviors. Together, these results suggest that the AOVP is involved in the generation of the aberrant defensive behaviors, and that 5-HT/DA balance is important in the regulation of social behaviors.

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adapted from the rat brain atlas (Paxinos and Watson 2009), and shows the six brain areas where c-Fos immunoreactive cells were counted and reported

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Acknowledgements

We particularly thank Dr. Aki Takahashi and Dr. Tsuyoshi Koide for their helpful comments on the experimental design. We also thank Dr. Ayuka Ehara for her experimental assistance and insightful discussions. We thank Bronwen Gardner, PhD, from Edanz Group (https://en-author-services.edanzgroup.com/) for editing a draft of this manuscript.

Funding

This work was supported by Grants-in-Aid for Scientific Research (C) (19K10256) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan.

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KN and US: conceived the study, designed the experiments, directed the project, and drafted the manuscript. Both authors read and approved the final manuscript.

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Correspondence to Nobuyuki Kai.

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The authors declare that they have no conflict of interest.

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All animal experiments were performed according to the guidelines established by the Animal Research Committee of Dokkyo Medical University (Tochigi, Japan).

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The datasets created and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Kai, N., Ueda, S. Induction of aberrant agonistic behavior by a combination of serotonergic and dopaminergic manipulation in rats. Brain Struct Funct 226, 1253–1267 (2021). https://doi.org/10.1007/s00429-021-02238-3

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  • DOI: https://doi.org/10.1007/s00429-021-02238-3

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