Psychopharmacological investigations of a lead-induced long-term cognitive deficit in monkeys

Abstract

This study investigated pharmacological manipulations of the cholinergic (ACh) and dopaminergic (DA) transmitter systems in monkeys with a long-term lead-induced cognitive deficit on delayed spatial alternation (DSA). Both ACh and DA have been found to be affected by developmental lead exposure and to be involved with performance on spatial learning and memory tasks. The lead-induced deficit in performance accuracy on DSA persisted throughout the 2 years of this experiment, which ended more than 8 years after the end of the postnatal lead exposure. Acute administration of agonists and antagonists of the ACh and DA systems did not elicit differential effects from the lead-exposed and control groups in terms of DSA per cent correct performance. The ACh antagonist, scopolamine, caused a dose-related decline in performance in both groups. Significant amelioration of the lead-induced DSA deficit was achieved by chronic treatment with the DA agonist, L-dopa. After withdrawal from L-dopa, the lead-related deficit reappeared. Improvement in performance of the lead-treated group was also seen after chronic amphetamine administration, but this effect was not significant. These data implicate DA mechanisms in the long-lasting cognitive effects of developmental lead exposure. The alleviation of the deficit with chronic administration of a DA precursor points to a possible line of treatment for the cognitive effects of developmental lead exposure.

Lifetime exposure to environmental lead and children's intelligence at 11-13 years: the Port Pirie cohort study

“…It has been shown that lead alters release processes for neuro-transmitters such as dopamine, norepinephrine, and acetylcholine by interfering with calcium metabolism or synaptic functioning, or both,40 41 42 and that lead exerts effects on the activities of such enzymes as kinase C, calmodulin, tyrosine hydroxylase, and choline acetyl-transferase, and also on brain energy metabolism 43 44 45. However, the direct relevance of these effects to the higher level processes of cognitive functioning assessed during developmental testing remains to be determined.…”

Behavioral effects of developmental lead exposure in rhesus monkeys

“…These results had suggested that certain of the cognitive deficits might be mediated by changes in attentional processes or distractability. In particular, the finding of a very long-lasting deficit on the learning and memory test, delayed spatial alternation, following pulse-chronic exposure during the first year implicated attentional deficits (Levin & Bowman, 1987). In that study, choice accuracy was most impaired by lead at the shortest intertrial delays, indicating that the deficit was probably not a result of memory impairment, leaving attentional impairment as a likely interpretation.…”

Lead and PCBs as Risk Factors for Attention Deficit/Hyperactivity Disorder

“…Despite differences in experimental procedures, developmentally lead-exposed monkeys in several studies conducted in two different labs were impaired in their ability to learn the DSA task (Levin and Bowman 1986; Levin et al 1987; Rice and Gilbert 1990a; Rice and Karpinski 1988). In both labs, lead-exposed monkeys were more likely to press the same lever repeatedly (perseverate) rather than alternate between levers.…”

“…Lead-exposed animals also have underlying neurochemical deficits that share commonalities with ADHD, including reduced dopamine signaling (e.g., Cory-Slechta 1997; Levin et al 1987). However, not all studies are concordant.…”