Behavioral responses to methylphenidate and apomorphine in rats exposed neonatally to bisphenol-A.

Abstract

Neonatal exposure of rats to bisphenol-A, an endocrine disruptor, has recently been proposed as a possible animal model of attention-deficit hyperactivity disorder, because such rats exhibit motor hyperactivity and impaired habituation to a novel environment 4-5 weeks after bisphenol-A pretreatment. To extend the original experiments, the present study additionally analyzed the effects of neonatal exposure to bisphenol-A (20 and 40 microg) on rat habituation to a novel environment and drug-induced behavior particularly at a later stage after bisphenol-A pretreatment. Single intracisternal administration of bisphenol-A (20 microg) into 5-day-old male Wistar rats did not cause any significant changes in habituation, as assessed in terms of locomotor activity, rearing, sniffing and grooming in rats at 8 weeks of age. Methylphenidate (1 and 3 mg/kg, i.p.), a psychostimulant, dose-dependently enhanced locomotor activity in both vehicle- and bisphenol-A (20 microg)-pretreated rats at 8 weeks of age, whereas other behaviors, i.e. rearing, sniffing and grooming, were not significantly affected. Additional challenge with apomorphine (1 mg/kg, i.v.), a dopamine receptor agonist, in vehicle- and bisphenol-A (20 and 40 microg)-pretreated rats at 10 weeks of age elicited a similar level of repetitive jaw movements measured by a magnet-sensing system under freely moving conditions during both the dark and the light phases. Thus, the effects of apomorphine did not differ between bisphenol-A-pretreated and vehicle-pretreated rats. It is concluded that, though some behavioral changes are evident in rats at an early stage (4-5 weeks) after neonatal treatment with bisphenol-A, the pretreatment does not induce any behavioral changes in habituation to a novel environment or in response to methylphenidate and to apomorphine at a later stage (8-10 weeks).