Effects of L-Dopa, SKF-38393, and quinpirole on exploratory, anxiety- and depressive-like behaviors in pubertal female and male mice.

Adolescence is a phase of substantial changes in the brain, characterized by maturational remodeling of many systems. This remodeling allows functional plasticity to adapt to a changing environment. The dopaminergic system is under morphological and physiological changes during this phase. In the present study, we investigated if changes in the dopaminergic tone alter mice behavior in a receptor and sex-specific manner, specifically at the beginning of the puberty period. We administered L-Dopa, SKF-38393 (D1 dopamine receptor agonist), and Quinpirole (D2 dopamine receptor agonist) and tested male and female mice's motor, anxiety- and depressive-like behavior. While females displayed an impaired exploratory drive, males presented an intense depressive-like response. Our results provide insights into the function of dopaminergic development in adolescent behavior and highlight the importance of studies in this time window with male and female subjects.

Early postnatal l-Dopa treatment causes behavioral alterations in female vs. male young adult Swiss mice.

Dopaminergic signaling and neurodevelopment alterations are associated with several neuropsychiatric disorders. Knockout mice for dopamine transporters (DAT) as well as site-specific knockout mice lacking dopaminergic D2 autoreceptors in dopaminergic neurons (DA-D2RKO) display behavioral alterations such as hyperlocomotion and abnormal prepulse inhibition. However, it is possible that dopaminergic imbalances may have different effects during varied neurodevelopmental windows. In our previous study, we observed that elevated levels of dopamine during the perinatal developmental window increased exploratory behavior of juvenile (4-week-old) Swiss female mice and impaired hedonic behavior in males. In this study, we investigated whether these behavioral alterations persist through young adulthood. In order to do so, we administered daily doses of l-Dopa to mice pups beginning from postnatal day 1 (PD1) to PD5. At the age of 8 weeks, we submitted the young adult males and females to the open field test, elevated plus maze, forced swimming test, and sucrose preference test. We observed that augmentation of dopamine levels during the perinatal developmental window increased locomotor behavior in females, but not males. We also observed an increase in anxiety-behavior in females and anxiolytic-like behavior in males. In addition, we observed stress-coping behavior in males and an increase of hedonic behavior in females. Our results show that dopamine signaling is important for behavioral development and that transient imbalances of dopamine levels can cause permanent behavioral alterations - alterations which are different in males than in females. These data may help in better understanding the spectrum of symptoms associated with different neuropsychiatric disorders.