Divergent anomaly in mesocorticolimbic dopaminergic circuits might be associated with different depressive behaviors,...

The mesocorticolimbic dopamine system, which originates from the ventral tegmental area (VTA) and projects primarily to the prefrontal cortex (PFC), olfactory tubercle (OT), nucleus accumbens (NAc), dorsal striatum (ST), and the amygdala (AMy), plays a pivotal role in determining individual motivation and sensitivity to rewards, namely, anhedonia. Not all depressive individuals exhibited anhedonia, thus, it is natural to speculate that the heterogenous manifestations of depression might be related to the mesocorticolimbic dopamine system. Maternal deprivation (MD) and chronic unpredictable stress (CUPS) are two well-established depressogenic stressors, and they were proven to induce different depressive phenotypes.

The depressive and anxiety-like behaviors of MD and CUPS-treated rats were measured by classical behavioral tests including open field, forced swimming, and sucrose preference test. The expression of D1-5 dopamine receptors and DAT mRNA and protein in the mesocorticolimbic dopamine system of rats exposed to MD and CUPS were measured by real-time PCR and Western blot, respectively.

Severe anhedonia was observed in MD but not CUPS rats. Divergent expression of D1 and D2 receptors and DAT mRNA and protein in the mesocorticolimbic dopamine system were found between MD and CUPS rats. Significant correlations between different depressive behaviors and D1-/D2-like receptors and DAT protein levels in the mesocorticolimbic dopamine system were observed.

Different depressive behaviors of rats such as anhedonia, passive coping behavior, and declined exploratory interest might be related to divergent dopaminergic pathways. Anhedonia is associated with the dysfunction of VTA-NAc and VTA-OT dopaminergic pathways, the passive coping behavior is related to the dysregulation of VTA-PFC and VTA-AMy pathways, and individual exploratory interest is associated with abnormal activity of VTA-PFC and VTA-ST pathways.