Development of adrenergic receptor binding sites in brain regions of the neonatal rat: effects of prenatal or postnatal exposure to methylmercury.

In order to understand the effects of developmental exposure to methylmercury on the ontogeny of synaptic function, we examined the impact of prenatal or postnatal exposure on acquisition of receptor binding sites for norepinephrine. The actions of the mercurial were both regionally- and receptor subtype-selective and depended upon the maturational profile of each region. alpha 1- alpha 2- and beta-receptor sites in the cerebellum, the region which develops last, were the most vulnerable to methylmercury. In contrast, the same receptor subtypes in the midbrain + brainstem, which develops earliest, were resistant to methylmercury. The cerebral cortex, which matures at a time midway between cerebellum and midbrain + brainstem, also displayed intermediate vulnerability to actions of methylmercury on receptors. Within the cerebellum, prenatal exposure to 1 mg/kg of methylmercury interfered the most with ontogeny of alpha 1-receptor binding, less so for alpha 2-receptors and least for beta-receptors. Lower doses of methylmercury tended to increase receptor binding for all subtypes, a fact which may contribute to promotion of neurological development seen in animals exposed to those levels. These data support the view that methylmercury exerts a dual spectrum of action on developing synapses, with promotional effects predominating at low doses and inhibitory actions at higher doses. The net effect on responsiveness to neurotransmitters is influenced, in part, by the actions on developing receptor sites which are in turn dependent upon the specific regional timetables for cellular maturation and receptor acquisition.

Duke Scholars

Author Theodore Alan Slotkin Pharmacology & Cancer Biology