title: Stimulation of postsynapse adrenergic α2A receptor improves attention/cognition performance in an animal model of attention deficit hyperactivity disorder.
abstract: A 5-trial inhibitory avoidance test using spontaneously hypertensive rat (SHR) pups has been used as an animal model of attention deficit hyperactivity disorder (ADHD). However, the roles of noradrenergic systems, which are involved in the pathophysiology of ADHD, have not been investigated in this model. In the present study, the effects of adrenergic α2 receptor stimulation, which has been an effective treatment for ADHD, on attention/cognition performance were investigated in this model. Moreover, neuronal mechanisms mediated through adrenergic α2 receptors were investigated. We evaluated the effects of both clonidine, a non-selective adrenergic α2 receptor agonist, and guanfacine, a selective adrenergic α2A receptor agonist, using a 5-trial inhibitory avoidance test with SHR pups. Juvenile SHR exhibited a shorter transfer latency, compared with juvenile Wistar Kyoto (WKY) rats. Both clonidine and guanfacine significantly prolonged the transfer latency of juvenile SHR. The effects of clonidine and guanfacine were significantly blocked by pretreatment with an adrenergic α2A receptor antagonist. In contrast, the effect of clonidine was not attenuated by pretreatment with an adrenergic α2B receptor antagonist, or an adrenergic α2C receptor antagonist, while it was attenuated by a non-selective adrenergic α2 receptor antagonist. Furthermore, the effects of neither clonidine nor guanfacine were blocked by pretreatment with a selective noradrenergic neurotoxin. These results suggest that the stimulation of the adrenergic α2A receptor improves the attention/cognition performance of juvenile SHR in the 5-trial inhibitory avoidance test and that postsynaptic, rather than presynaptic, adrenergic α2A receptor is involved in this effect.
authors.affiliation: Pharmacology I, Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kawaura
authors.affiliation: Pharmacology I, Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Karasawa
authors.affiliation: Pharmacology I, Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Chaki
authors.affiliation: Pharmacology I, Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan. Electronic address: h-hikichi@so.taisho.co.jp.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Hikichi
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001288:Attention / Q000187:drug effects*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology; D001362:Avoidance Learning / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D016316:Guanfacine / Q000494:pharmacology; D007266:Inhibition, Psychological; D008297:Male; D009483:Neuropsychological Tests; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D016896:Treatment Outcome
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D016316:Guanfacine; D003000:Clonidine
keywords: 5-Trial inhibitory avoidance test; Adrenergic α(2A) receptor; Attention deficit hyperactivity disorder; Clonidine; Guanfacine; Juvenile spontaneously hypertensive rat