Effect of methylphenidate on c-Fos expression in parvalbumin interneurons of juvenile rat frontal cortex / 生理学报

ABSTRACT

The etiology of attention-deficit hyperactivity disorder (ADHD) has been generally linked to the decrease in cortex activity, as well as to the reduction in dopamine (DA) and norepinephrine (NE) levels. Methylphenidate (MPH; Ritalin) is the most commonly prescribed medication for ADHD. It has been determined that MPH acts primarily on the dopaminergic and noradrenergic systems through blockade of DA and NE transporters, thereby increasing the concentrations of these neurotransmitters in the brain to correct the attention deficits and hyperactivity. In addition, MPH has been proposed to increase the excitability of pyramidal neurons and the overall activity of cortex. However, the effect of MPH on the activity of interneurons is lack of investigation. Here, by using immunohistochemistry technique, we examined c-Fos expression in parvalbumin (PV)-expressing interneurons of frontal cortex of rats (28-day-old) at 1 h after a single MPH infusion (1 or 8 mg/kg; s.c.). We analyzed the c-Fos expression in the medial orbitofrontal cortex (MO), ventral orbitofrontal cortex (VO), and lateral orbitofrontal cortex (LO) subregions of orbitofrontal cortex (OFC), as well as the prelimbic cortex (PrL) and infralimbic cortex (IL) subregions of the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) after MPH infusion. Our data showed that MPH increased c-Fos expression in MO, VO and LO, and the c-Fos expression in PV-expressing interneurons elevated significantly in MO, VO, but not in LO. Meanwhile, the increases of c-Fos expression in PrL and IL, as well as in PV-expressing interneurons of these two regions, were only induced by 1 mg/kg MPH, but not 8 mg/kg. Both 1 and 8 mg/kg MPH dramatically increased c-Fos expression in ACC, especially, in PV-expressing interneurons of ACC as well. In conclusion, acute systemic injection of MPH significantly increases the c-Fos expression in PV-expressing interneurons of the OFC, PFC and ACC.