Lead (Pb(+2)) impairs long-term memory and blocks learning-induced increases in hippocampal protein kinase C activity.

The long-term storage of information in the brain known as long-term memory (LTM) depends on a variety of intracellular signaling cascades utilizing calcium (Ca2+) and cyclic adenosine monophosphate as second messengers. In particular, Ca(+2)/phospholipid-dependent protein kinase C (PKC) activity has been proposed to be necessary for the transition from short-term memory to LTM. Because the neurobehavioral toxicity of lead (Pb(+2)) has been associated to its interference with normal Ca(+2) signaling in neurons, we studied its effects on spatial learning and memory using a hippocampal-dependent discrimination task. Adult rats received microinfusions of either Na+ or Pb(+2) acetate in the CA1 hippocampal subregion before each one of four training sessions. A retention test was given 7 days later to examine LTM. Results suggest that intrahippocampal Pb(+2) did not affect learning of the task, but significantly impaired retention. The effects of Pb(+2) selectively impaired reference memory measured in the retention test, but had no effect on the general performance because it did not affect the latency to complete the task during the test. Finally, we examined the effects of Pb(+2) on the induction of hippocampal Ca(+2)/phospholipid-dependent PKC activity during acquisition training. The results showed that Pb(+2) interfered with the learning-induced activation of Ca(+2)/phospholipid-dependent PKC on day 3 of acquisition. Overall, our results indicate that Pb(+2) causes cognitive impairments in adult rats and that such effects might be subserved by interference with Ca(+2)-related signaling mechanisms required for normal LTM.