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[Effect of methylphenidate on c-Fos expression in parvalbumin interneurons of juvenile rat frontal cortex]
Ying-Chun Zhang1, Xue-Qing Zhu1, Xue-Han Zhang2
1Institutes of Brain Science, Fudan University, Shanghai 200032, China.
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.
Insights
Methylphenidate (MPH) increases brain activity in specific regions of the cortex, particularly in parvalbumin-expressing interneurons. This study investigated MPH's effects on these neurons in attention-deficit hyperactivity disorder (ADHD) models.
Area of Science:
- Neuroscience
- Pharmacology
- Neurobiology
Background:
- Attention-deficit hyperactivity disorder (ADHD) is linked to reduced cortex activity and lower dopamine (DA) and norepinephrine (NE) levels.
- Methylphenidate (MPH), a common ADHD medication, increases DA and NE by blocking transporters, enhancing cortical activity.
- The impact of MPH on interneuron activity, crucial for cortical regulation, remains under-investigated.
Purpose of the Study:
- To examine the effect of acute methylphenidate (MPH) administration on c-Fos expression in parvalbumin (PV)-expressing interneurons within specific rat frontal cortex regions.
- To investigate dose-dependent effects of MPH on neuronal activity in the orbitofrontal cortex (OFC), prefrontal cortex (PFC), and anterior cingulate cortex (ACC).
Main Methods:
- Immunohistochemistry was used to detect c-Fos expression, a marker of neuronal activity.
- 28-day-old rats received single subcutaneous injections of MPH (1 or 8 mg/kg).
- c-Fos expression was analyzed in PV-interneurons of the medial, ventral, and lateral orbitofrontal cortex (MO, VO, LO), prelimbic (PrL), infralimbic (IL), and anterior cingulate cortex (ACC).
Main Results:
- MPH increased overall c-Fos expression in MO, VO, and LO, with significant increases in PV-interneurons in MO and VO.
- Low-dose MPH (1 mg/kg) increased c-Fos in PrL and IL, including PV-interneurons, an effect not seen with high-dose MPH (8 mg/kg).
- Both MPH doses significantly elevated c-Fos expression in the ACC, particularly in PV-interneurons.
Conclusions:
- Acute MPH administration significantly increases neuronal activity, specifically in parvalbumin-expressing interneurons, across the OFC, PFC, and ACC.
- These findings highlight MPH's complex effects on cortical interneuron populations, potentially contributing to its therapeutic mechanisms in ADHD.
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