Abstract：Objective To investigate the ideal animal models for attention deficit hyperactivity disorder (ADHD) subtypes and the effect of glucocorticoid receptor (GR) function on the behavior of ADHD rats by comparing behavioral differences between spontaneously hypertensive rats (SHRs), Wistar Kyoto (WKY) rats, and Sprague-Dawley (SD) rats. Methods A total of 24 male SHRs aged 21 days were randomly divided into GR agonist group, GR inhibitor group, and SHR group, with 8 rats in each group. Eight male WKY rats and 8 male SD rats, also aged 21 days, were enrolled as WKY group and SD group respectively. The GR agonist group was treated with intraperitoneal injection of dexamethasone (0.5 mg/kg daily); the GR inhibitor group was treated with intraperitoneal injection of mifepristone (RU486)(54 mg/kg daily); the SHR, WKY, and SD groups were treated with intraperitoneal injection of normal saline (0.5 mL/kg daily). The course of treatment was 14 days for all groups. The open field test and Lat maze test were used to evaluate spontaneous activity and non-selective attention. Results The open field test showed that before drug intervention the SHR group had significantly higher numbers of line crossings and rearings than the WKY and SD groups (P < 0.05); the WKY group had a significantly higher number of line crossings than the SD group (P < 0.05); the SD group had a significantly higher number of groomings than the WKY group (P < 0.05). After drug intervention, the GR agonist group had significantly lower numbers of line crossings and groomings than the SHR group (P < 0.05). The Lat maze test indicated that before drug intervention the SHR group had significantly higher numbers of corner crossings and rearings than the WKY and SD groups (P < 0.05); the WKY group had significantly higher numbers of rearings and leanings than the SD group (P < 0.05). After drug intervention, the GR agonist group had significantly lower numbers of corner crossings and rearings than the SHR group (P < 0.05); the GR inhibitor group had a significantly higher number of rearings than the SHR group (P < 0.05); the WKY group had significantly higher numbers of rearings and leanings than the SD group (P < 0.05). Conclusions SHR is an ideal animal model for mixed subtype ADHD, and further studies are needed to determine whether WKY rats can be used as an animal model for attention-deficit subtype ADHD. GR agonist can effectively improve spontaneous activity and non-selective attention in SHRs.
LU Hong-Zhu,ZHANG Fei-Xia,HONG Xiao-Wen et al. Effect of glucocorticoid receptor function on the behavior of rats with attention deficit hyperactivity disorder[J]. CJCP, 2018, 20(10): 848-853.
Willcutt EG. The prevalence of DSM-IV attentiondeficit/hyperactivity disorder:a meta-analytic review[J]. Neurotherapeutics, 2012, 9(3):490-499.
[2]
Polanczyk GV, Salum GA, Sugaya LS, et al. Annual research review:a meta-analysis of the worldwide prevalence of mental disorders in children and adolescents[J]. J Child Psychol Psychiatry, 2015, 56(3):345-365.
[3]
Isaksson J, Hogmark Å, Nilsson KW, et al. Effects of stimulants and atomoxetine on cortisol levels in children with ADHD[J]. Psychiatry Res, 2013, 209(3):740-741.
Senft RA, Meddle SL, Baugh AT. Distribution and abundance of glucocorticoid and mineralocorticoid receptors throughout the brain of the great tit (parus major)[J]. PLoS One, 2016, 11(2):e0148516.
Rezaei G, Hosseini SA, Akbari Sari A, et al. Comparative efficacy of methylphenidate and atomoxetine in the treatment of attention deficit hyperactivity disorder in children and adolescents:a systematic review and meta-analysis[J]. Med J Islam Repub Iran, 2016, 30:325.
[10]
Carvalho C, Vieira Crespo M, Ferreira Bastos L, et al. Contribution of animal models to contemporary understanding of Attention Deficit Hyperactivity Disorder[J]. ALTEX, 2016, 33(3):243-249.
[11]
Somkuwar SS, Jordan CJ, Kantak KM, et al. Adolescent atomoxetine treatment in a rodent model of ADHD:effects on cocaine self-administration and dopamine transporters in frontostriatal regions[J]. Neuropsychopharmacology, 2013, 38(13):2588-2597.
[12]
Fox MA, Panessiti MG, Hall FS, et al. An evaluation of the serotonin system and perseverative, compulsive, stereotypical, and hyperactive behaviors in dopamine transporter (DAT) knockout mice[J]. Psychopharmacology (Berl), 2013, 227(4):685-695.
[13]
Miller EM, Pomerleau F, Huettl P, et al. The spontaneously hypertensive and Wistar Kyoto rat models of ADHD exhibit sub-regional differences in dopamine release and uptake in the striatum and nucleus accumbens[J]. Neuropharmacology, 2012, 63(8):1327-1334.
Banegas I, Prieto I, Segarra AB, et al. Bilateral distribution of enkephalinase activity in the medial prefrontal cortex differs between WKY and SHR rats unilaterally lesioned with 6-hydroxydopamine[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2017, 75:213-218.
King LS, Colich NL, LeMoult J, et al. The impact of the severity of early life stress on diurnal cortisol:the role of puberty[J]. Psychoneuroendocrinology, 2017, 77:68-74.
[19]
Isaksson J, Allen M, Nilsson KW, et al. Polymorphisms in the FK506 binding protein 5 gene are associated with attention deficit hyperactivity disorder and diurnal cortisol levels[J]. Acta Paediatr, 2015, 104(9):910-915.
[20]
Ma L, Chen YH, Chen H, et al. The function of hypothalamuspituitary-adrenal axis in children with ADHD[J]. Brain Res, 2011, 1368:159-162.
[21]
Isaksson J, Nilsson KW, Nyberg F, et al. Cortisol levels in children with attention-deficit/hyperactivity disorder[J]. J Psychiatr Res, 2012, 46(11):1398-1405.
