Abstract
Recently, neuropsychological and pharmacological studies provide compelling supports for a central noradrenergic hypothesis in the pathophysiology of attention deficit / hyperactivity disorder (AD/HD) that is a development disorder of children. Therefore, the nucleus locus coeruleus (LC) where is the most major source of noradrenergic tone in a central nervous system is explored to examine the effect of methylphenidate (MPH), since MPH is the most commonly used agent for a treatment of AD/HD. In the present study, the effect of MPH on neural activity of the LC of juvenile rats was examined by using a whole-cell patch clamp technique. MPH caused an outward current associated with an increase in inward rectifier K+ channels. MPH significantly potentiated the amplitude and time course of slow IPSCs in LC neurons, although MPH did not affect EPSCs. MPH increased the amplitude of slow IPSCs in a dose dependent manner (0.3< MPH< 3 μM), however higher dose of MPH (> 10 μM) contrary inhibited slow IPSCs. MPH enhanced the amplitude of miniature IPSCs in presence of TTX. These results were the same as the data from adult rats. Further more, noradrenalin (NA) content in a brain slice preparation was measured with and without MPH treatment by HPLC. On the LC of juvenile rats as well as adult rats, MPH may enhance the concentration of NA in the synapscleft as NA re-uptake blocker. These results suggest that noradrenergic agents play the important role in the therapy of AD/HD. [Jpn J Physiol 54 Suppl:S149 (2004)]
