Behavioural characterisation of rats exposed neonatally to bisphenol-A: responses to a novel environment and to methylphenidate challenge in a putative model of attention-deficit hyperactivity disorder
Neonatal exposure of rats to bisphenol-A, an endocrine disruptor, has recently been proposed as a possible animal model of attention-deficit hyperactivity disorder (ADHD), because such rats exhibit motor hyperactivity. To strengthen the face validity of this animal model, the present study replicated the original experiments and additionally analysed both changes in habituation to a novel environment and behavioural responses to methylphenidate, the two phenomena known to be altered in ADHD. Single intracisternal administration of bisphenol-A (20 and 40 μg) into 5-day-old male Wistar rats impaired habituation to a novel environment in the light, but not the dark, phase at 4 weeks of age. Thus, habituation as assessed by time-dependent decrease of locomotor activity, rearing, sniffing and grooming was significantly reduced in bisphenol-A-pretreated rats. Methylphenidate (1 and 3 mg/kg, i.p.) dose-dependently enhanced locomotor activity in both vehicle-pretreated and bisphenol-A-pretreated rats during both the dark and the light phases. Thus, the effects of methylphenidate did not differ between bisphenol-A-pretreated and vehicle-pretreated rats. Apart from a slight methylphenidate-induced increase in rearing and sniffing in bisphenol-A (20 μg)-pretreated rats, the overall effects of methylphenidate on rearing, sniffing and grooming were similar in both vehicle- and bisphenol-A-pretreated rats. It is concluded that neonatal exposure of rats to bisphenol-A is an animal model with limited face validity for ADHD, because the motor hyperactivity and reduced habituation to a novel environment are not accompanied by altered responses to methylphenidate.
KeywordsNeonatal endocrine disruptor Attention-deficit hyperactivity disorder Habituation Locomotor activity Rearing Sniffing Grooming Animal model Rodents
We thank Dr. Yoshinori Masuo for his technical guidance regarding intracisternal injections of bisphenol-A to pups. These studies were supported by the Sato Fund (NK), Uemura Fund (NK) and Dental Research Centre (HO, NK) at Nihon University School of Dentistry; the Promotion and Mutual Aid Corporation for Private Schools of Japan (MK, NK); and a “Kakenhi” for Young Scientists (B, # 17791332 to SF) and a grant for promotion of multidisciplinary research projects entitled “Translational Research Network on Orofacial Neurological Disorders” (NK, ARC) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
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