Abstract
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-HT(2) 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-HT(2) 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-HT(2) densities, respectively. Rats presented a more widespread range of significant differences concerning the ratio between 5-HT(1A) and 5-HT(2) receptors across examined areas than did humans. Concluding, this comparative study reveals species differences in 5-HT(1A) and 5-HT(2) 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.