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

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.