PRENATAL ADMINISTRATION OF 5-HT PRECURSOR ALTERS BEHAVIOR IN ADULT WILD TYPE MICE AND IN A MOUSE MODEL OF ADHD

Adverse prenatal environment has been suggested as a risk factor for developing several neuropsychiatric disorders. Previous studies have indicated 5-HT as a powerful modulator of development and that both too low or too high placental levels can modify disease occurrence. In the current study we administrated prenatally the precursor of 5-HT, 5-HTP, on gestational days 11-14 of wild type (WT) and DAT-flp heterozygous (HET) mice that we used as an animal model of ADHD. We then monitored the behavior of offspring in adulthood by performing a series of tasks assessing locomotor, anxiety and social behavior. We found that HET mice showed increased locomotion in the open field and deficits in sociability, measured in the three-chamber social interaction test. Treatment with 5-HTP did not alter the locomotor activity in HET mice but decreased it in WT mice, and induced anxiolytic and anxiogenic effects in WT male and female HET mice, respectively. In the social domain, the treatment rescued the HET phenotype only in male mice but induced a deficit in WT female mice, while having no effect in HET female mice. In the same task, treated WT male mice showed increased interaction with a novel individual. In the social habituation-dishabituation test we confirmed that treated HET female mice spent less time interacting with the stimuli mice while male WT treated mice spent more time interacting with novel mice. Our results point out that prenatal elevations of 5-HT can have both beneficial and detrimental effects in a genotype- and sex-dependent manner.