Effect of methylphenidate treatment during adolescence on norepinephrine transporter function in orbitofrontal cortex in a rat model of attention deficit hyperactivity disorder

摘要: Attention deficit hyperactivity disorder (ADHD) is associated with hypofunctional medial prefrontal cortex (mPFC) and orbitofrontal (OFC). Methylphenidate (MPH) remediates ADHD, in part, by inhibiting the norepinephrine transporter (NET). MPH also reduces ADHD-like symptoms spontaneously hypertensive rats (SHRs), a model of ADHD. However, effects chronic treatment on NET function mPFC OFC SHR have not been reported. In current study, long-term repeated therapeutically relevant oral dose during adolescence subregions (cingulate gyrus, prelimbic infralimbic cortex) adult SHR, Wistar-Kyoto (WKY, inbred control) Wistar (WIS, outbred were determined using vivo voltammetry. Following local ejection (NE), uptake rate was as peak amplitude (Amax) × first-order constant (k−1). subregions, no strain or found NE rate. OFC, vehicle-treated greater than WKY WIS administered vehicle. normalized SHR. Thus, study implicates increased an underlying mechanism for reduced noradrenergic transmission consequently, behavioral deficits adulthood, suggesting that therapeutic action persists long after cessation may contribute to lasting reductions