ADHD is a common psychiatric disorder in children. It currently affects about 5 percent of children globally and often continues as a chronic disorder in adulthood. It is characterized by attention difficulties and hyperactivity, which cause burden to suffering individuals.
ADHD has a strong genetic component, and there is a two-fold greater prevalence in males than females. So far, all drug treatments for ADHD target monoamine-releasing neurons in the brain. The psychostimulants d-amphetamine and methylphenidate are widely used, but due to the nature of these drugs there is some unease about giving them to children. Therefore, development of alternative drug treatments that are more effective, potentially less addictive, and have fewer side effects would be an important advance.
NK1R-/- Mouse
NK1R-/- mice, which lack functional substance P-preferring NK1 receptors (NK1R), display locomotor hyperactivity. This is prevented by psychostimulants [e.g., d-amphetamine (d-AMP)], as in patients with ADHD. Regulation of noradrenaline (NA) and serotonin (5-HT) release is impaired in NK1R-/- mice (Froger et al, 2001, Herpfer et al, 2005; Fisher et al, 2007).
NK1R-/- mice have been shown to have abnormalities in NA and dopamine (DA) efflux in their prefrontal cortex (PFC) and/or dorsal striatum by using in vivo microdialysis. In addition, these mice have behavioral abnormalities resembling diagnostic features of ADHD: inattentiveness, impulsivity and perseveration. These behaviors can be reversed by d-amphetamine and methylphenidate.
For more information about our NK1R-/- mouse model for ADHD research, please contact us at askcharlesriver@crl.com.