Effects of exposure to a predator on behaviour and serotonergic neurotransmission in different brain regions of C57bl/6N mice

Clinical studies and animal models have provided evidence that stress and serotonin may play a role in the aetiology of psychiatric diseases such as depression and anxiety. In addition, reciprocal interactions between stress and serotonergic neurotransmission have been demonstrated. However, the relationships between stress, serotonin and behaviour are far from completely understood. In this integrative study, we aimed to elucidate the effect of the psychological stress model predator exposure on behaviour and serotonergic neurotransmission in mice. We used a high time-resolution microdialysis method to measure extracellular levels of serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus, prefrontal cortex, lateral septum and caudate putamen of C57BL/6N [corrected] mice, before (08:30-10:30 h), during (10:30-11:00 h) and after exposure (11:00-14:00 h) to a rat. Detailed behavioural observations were also made. Rat exposure resulted in behavioural activation, with predominant risk-assessment activities, and in increases in hippocampal, cortical, septal but not striatal 5-HT and 5-HIAA. When rat exposure was repeated on the consecutive day, small behavioural differences and reductions in 5-HIAA levels, but no differences in the 5-HT response, as compared with the first exposure were observed. As increases in 5-HT often coincide with behavioural activation, it was particularly interesting to find that 5-HT also increased in periods when mice only made minor movements such as sniffing, and that an effect of predator stress was absent in the caudate putamen. Our results indicate that the presence of the rat leads to differential activation of serotonergic neurotransmission in higher brain structures, probably involved in the coping response to this potentially life-threatening situation.