Regional brain and pituitary cyclic nucleotide response following central cholinergic stimulation in rats chronically exposed to lead.

Long Evans rats were exposed continuously to lead (1,000 ppm of lead acetate in the drinking water of dam or weanling) throughout gestation, lactation and until sacrifice at 60 days of age. A matched group of control animals was exposed to distilled water. On the day of sacrifice, control and lead treated animals were administered methylatropine 40 min. and oxotremorine (a muscarinic agonist) 10 min. prior to sacrifice by microwave irradiation. Locomotor activity was monitored during the 10 min. immediately preceding sacrifice. Levels of cyclic AMP and cyclic GMP were determined in 21 brain regions by radioimmunoassay. Locomotor activity following oxotremorine was significantly reduced in both lead treated and control animals. Levels of cyclic GMP were increased in septal region and frontal cortex and reduced in cerebellum and inferior colliculus of both groups of animals. The level of cyclic AMP in the pituitary increased 20-25 fold with a greater response noted in lead treated rats. Elevations of cyclic AMP were also noted in the interpeduncular nucleus, corpus striatum and substantia nigra in both groups. These data suggest that the cellular response to a muscarinic agonist was significantly affected by chronic exposure to lead in the pituitary but not in the remainder of the central nervous system.