Role of Locus Coeruleus Chemogenetic Modulation in the Behavior of Hyperdopaminergic Rats Lacking the Dopamine Transporter

The Locus Coeruleus (LC) is a critical area in the brain that plays an important role in several neural pathways associated with a range of physiological and behavioral processes. Its activity can modulate both norepinephrine (NE) and dopamine neurotransmission, particularly in the prefrontal cortex (PFC). In the present study, we show that a chemogenetically induced increase in norepinephrine release from the LC to the PFC reduced hyperactive behavioral patterns in rats lacking the dopamine transporter (DAT-KO rats) with spontaneously elevated dopamine transmission. These manipulations in hyperdopaminergic mutants also caused amelioration of cognitive abnormalities in spatial learning task as evidenced by decreases in perseverative activity and the number of visits to the error zone. Furthermore, chemogenetic activation of NE neurotransmission in these animals significantly improved their performance in in this maze test. Thus, the results obtained of this study highlight an important modulatory role of NE on hyperactivity and cognitive dysfunctions of hyperdopaminergic DAT-KO rats lacking the dopamine transporter.