Abnormal Behavior of Dopamine Transporter Knockout Rats During Early Ontogeny

The dopamine (DA) hypothesis of attention deficit hyperactivity disorder (ADHD) is the most experimentally supported; however, up until recently, it was primarily based on neuropharmacological studies showing that monoamine-activating drugs effectively treat this disorder's symptoms. It is therefore essential to determine the specific mechanisms involved in the association between DA system dysfunction and ADHD. This study examined how the absence of the dopamine transporter (DAT) influences neurobehavioral maturation in neonatal rats. Rat pups of three genotypes-DAT-KO (knockout), DAT-HET (heterozygous), and DAT-WT (wild type) rats-underwent a battery of neurobehavioral tests, including surface righting reflex, negative geotaxis, cliff avoidance, eye opening, auditory startle response, olfactory discrimination, air righting reflex, and Morris Water Maze. Knockout of the Dat gene significantly delayed the acquisition of surface righting, negative geotaxis, cliff avoidance, and air righting reflexes compared with WT controls, whereas the timing of eye opening, auditory startle response, and olfactory discrimination was unaffected. Our study provides the first evidence that Dat knockout alters neurobehavioral development in 0-5-week-old rat pups. These findings highlight the importance of investigating the effects of genetic manipulation of DA system on behavioral development and strengthen the validity of the DAT-KO model for studying ADHD.