AD/HDモデル:高血圧自然発症ラット (SHR) の青斑核ニューロンにおける自発活動は減弱している

抄録

The main problem of attention deficit/hyperactivity disorder (AD/HD), one of developmental disorders of children, is difficulty in control or restrain of behavior. An imbalance of dopaminergic and noradrenergic transmission is proposed for neural mechanisms of AD/HD. On adult rats, we have already reported that methylphenidate, the most common therapeutic agent for AD/HD produced a hyperpolarizing response associated with decrease in a membrane resistance by activation of the inward rectifier K ⁺ channels via α₂-adrenoceptor of locus coeruleus (LC) neurons where the most major source of noradrenergic tones in CNS. The spontaneously hypertensive rat (SHR) are often used as a model of AD/HD. Behavioral studies established that SHR displayed hyperactivity, impulsivity, poor stability of performance and poorly sustained attention, when compared with their normotensive Wistar-Kyoto (WKY) control rats. In the present study, the tonic activity of LC neurons of juvenile SHR was examined by using a whole-cell patch clamp technique and compared with WKY. As a result, the resting membrane potential of LC neurons in SHR (-47.7±0.39 mV) was significantly decreased when compared with WKY (-51.4±0.63 mV). Nevertheless, the frequency of spontaneous action potentials of SHR (0.64±0.24 Hz) was significantly lower than that of WKY (2.14±0.53 Hz). These results suggest that noradrenergic spontaneous activity on LC neurons in SHR is reduced compare with WKY. [J Physiol Sci. 2006;56 Suppl:S173]