Serotonin Receptors in Areas of the Emotion Regulation Network in Human and Rat Brains—A Comparative Autoradiographic Study

Serotonergic neurotransmission is crucial for emotion processing and is dysregulated in mood disorders. To analyze the pathophysiology of disease and develop effective pharmacological treatments, the suitability of the rat as a model for translational research must be continuously validated. In vitro receptor autoradiography was used to characterize (dis)similarities of regional and laminar serotonergic 5-HT_1A and 5-HT₂ receptor distributions between components of the human emotion regulation network and homologous rat areas, including areas of the lateral prefrontal, orbitofrontal anterior and midcingulate cortices, hippocampal cornu Ammonis (CA) and dentate gyrus (DG), and the accumbens, central amygdaloid, and mediodorsal thalamic nuclei. In both species, mean 5-HT_1A densities were highest in cingulate area 25/infralimbic cortex and the hippocampus, and lowest in the accumbens. Whereas human CA presented significantly higher 5-HT_1A density than DG, the opposite was found in rats. Across the cortical depth, in humans, layers I–III and V contained the highest and lowest 5-HT_1A densities, respectively. In rats, layers I–II contained the lowest and layers V–VI the highest 5-HT_1A values. Mean 5-HT₂ densities were lower than 5-HT_1A densities in all areas of both species, whereby layers III and VI contained the highest and lowest 5-HT₂ densities, respectively. Rats presented a more widespread range of significant differences concerning the ratio between 5-HT_1A and 5-HT₂ receptors across examined areas than did humans. Concluding, this comparative study reveals species differences in 5-HT_1A and 5-HT₂ receptor densities in components of the emotion regulation network, which should be considered when using the rat as a model in the translational research of mood disorders.