Attention-deficit/hyperactivity disorder (AD/HD) is an early-onset neuropsychiatric disorder characterized by inattention, hyperactivity and impulsivity. We have previously proposed adolescent stroke-prone spontaneously hypertensive rats (SHRSP/Ezo) as an appropriate animal model of AD/HD, based on symptomatic features. Recently, guanfacine, a selective agonist of adrenergic α2A receptors, has been developed for the AD/HD treatment, which is expected as an alternative to a psychostimulant methylphenidate and a selective noradrenaline reuptake inhibitor atomoxetine. In this study, we investigated the effects of adrenergic α₂ receptor agonists on ADHD-like behavioral abnormalities in an animal model for AD/HD, male adolescent SHRSP/Ezo.
Six-week-old male SHRSP/Ezo (SHRSP) were bred in our laboratory. Age-matched Wistar-Kyoto rats (WKY/Ezo: WKY) were used as genetic controls. Guanfacine or clonidine was intraperitoneally administered 30min before the behavioral test.
SHRSP demonstrated the impaired alternative performance in the Y-maze test (attentional dysfunction) compared to WKY, which was ameliorated by guanfacine, a selective adrenergic α_2A receptor agonist, in a dose-dependent manner. Moreover, guanfacine markedly inhibited hyperactivity evaluated in the openfield test, and attenuated the increased time spent in the open arms in the elevated plus-maze test (impulsive-like behavior), observed in SHRSP. On the other hand, AD/HD-like behaviors (attentional dysfunction, hyperactivity and impulsive-like behavior) in SHRSP were also ameliorated by clonidine, a non-selective adrenergic α₂ receptor agonist, in a dose-dependent manner.
The present study demonstrated that attentional dysfunction, hyperactivity and impulsive-like behavior in SHRSP were ameliorated by both guanfacine and clonidine, adrenergic α₂ receptor agonists. Since guanfacine has already been clinically prescribed as a therapeutic drug for pharmacotherapy of AD/HD, our findings verified the further pharmacological validity as an AD/HD model animal in male adolescent SHRSP/Ezo.