マウス前頭前皮質におけるシナプス伝達に対するグアンファシン慢性投与の作用

抄録

The prefrontal cortex (PFC) is considered a potential contributor to attention deficit hyperactivity disorder (ADHD), a neurodevelopmental disorder, because the PFC regulates high-order cognitive functions, including attention and planning through working memory. As a medication for ADHD, the α_2A-adrenergic receptor (AR) agonist guanfacine (GFC) has been shown to improve PFC cognitive function, although the mechanisms of action of GFC within the PFC neuronal functions remains unknown. Previously we showed the acute GFC-induced target cell-dependent inhibition in glutamatergic synaptic transmission in the PFC. Thus, significant effect was observed by the acute GFC administration (aGFC) only in callosal/commissural-type (COM) neurons, but not corticopontine-projecting-type (CPn) neurons. On the other hand, GABAergic IPSCs were comparably inhibited in both types of neurons. In this study, we examined whether chronic GFC administration (cGFC) mimicking clinical use affects the neuronal and synaptic properties as observed in the aGFC. cGFC (0.3 and 1 mg/kg) for ~3 weeks using osmotic pump did not alter the membrane properties of CPn neurons. GFC-induced inhibitory action on EPSC amplitude was not affected either by cGFC. Based on these results, we conclude that cGFC did not alter at least the membrane properties of CPn neurons or dynamics of α₂-AR at glutamatergic synaptic terminals. We are currently analyzing the membrane properties of COM neurons and GABAergic synaptic transmission to further clarify the effect of cGFC observed in clinical use.