A selective decrease of cholinergic muscarinic receptors in the visual cortex of adult rats following developmental lead exposure

The effects of low-level developmental lead (Pb) exposure (postnatal days 0-21) on the binding of [3H]quinuclidinylbenzilate (QNB) and on acetylcholinesterase (AChE) activity in the retina, superior colliculus, lateral geniculate nucleus and visual cortex (VC) were studied in the adult rat. Maximal blood and tissue Pb concentrations (50-60 micrograms %) were reached on day 21 and decreased to control levels (4-5 micrograms %), except in the retina (12 micrograms %) and VC (18 micrograms %; 0.87 microM), by day 90. A large decrease in [3H]QNB binding (-38%) and AChE activity (-29%) was found only in the VC of Pb-exposed rats. Scatchard plots of saturation binding data revealed a decrease in the density (Bmax), but not in the affinity (Kd), of the muscarinic receptors. Pb (10(-4)-10(-9)M) had no effect on [3H]QNB binding or AChE activity in VC membrane preparations from control rats. The mechanism accounting for this selective decrease of cholinergic muscarinic receptors in the VC is presently unknown. These results, in combination with those from our psychophysical and pharmacological studies demonstrating a scopolamine supersensitivity in Pb-exposed rats, suggest that the long-term effects of developmental Pb exposure are due to a direct action of Pb on visual cortex cholinergic neurons.