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Postnatal lead exposure and the cholinergic system
Insights
Early lead (Pb) exposure in rats impaired learning and memory. Cholinergic drug treatments reversed these effects, suggesting lead-induced behavioral changes stem from impaired cholinergic function.
Area of Science:
- Neuroscience
- Toxicology
- Behavioral Science
Background:
- Early lead (Pb) exposure is linked to behavioral deficits.
- Cholinergic system dysfunction has been proposed as a mechanism for these effects.
Purpose of the Study:
- To investigate the role of cholinergic function in the behavioral effects of early lead exposure.
- To determine if modulating cholinergic activity can ameliorate lead-induced behavioral impairments.
Main Methods:
- Long-Evans hooded rat pups were exposed to lead (High Pb, low Pb, or control) via maternal milk for 25 days.
- Animals were behaviorally tested at 65 days of age using tasks assessing passive avoidance, spontaneous alternation, and open field activity.
- The effects of cholinergic agonist (physostigmine) and antagonist (scopolamine) were examined in control and lead-exposed rats.
Main Results:
- Lead exposure impaired passive avoidance acquisition and spontaneous alternation but not open field activity.
- Physostigmine improved behavioral deficits in lead-exposed rats.
- Scopolamine mimicked some lead-induced deficits in control rats and showed complex effects in lead-exposed rats, suggesting an inverted U-shaped dose-response.
Conclusions:
- Behavioral responses of lead-exposed rats are consistent with cholinergic deficiency.
- These findings provide further evidence for the involvement of the cholinergic system in the behavioral consequences of early lead exposure.
Abstract:
Previous reports have suggested that the behavioral effects of early lead (Pb) exposure may be due to an underlying deficiency in cholinergic function. To further examine this possibility, Long-Evans hooded rat pups were exposed to Pb for the first 25 postnatal days via the maternal milk. Dams were fed either 4.0% PbCO3 (High Pb), 0.4% PbCO3 (low Pb) or a Na2CO3 control diet throughout this period. Beginning at 65 days of age, animals were tested on behavioral tasks sensitive to both Pb exposure and cholinergic deficiency. Exposure to both levels of Pb impaired passive avoidance acquisition and produced lower rates of spontaneous alternation. Pb, however, had no clear effects on open field activity. The cholinergic agonist physostigmine (0.05 and 0.075 mg/kg) did not affect the behavior of control animals on any task, but in both Pb exposed groups physostigmine improved passive avoidance acquisition, increased the rate of spontaneous alternation and lowered open field activity scores. The cholinergic antagonist scopolamine (0.4 mg/kg) impaired passive avoidance acquisition, lowered the rate of spontaneous alternation and increased open field activity scores in control animals. Consistent with behavior characteristic of an inverted U shaped response curve, scopolamine (0.2 and 0.4 mg/kg) improved passive avoidance acquisition in both Pb exposed groups and decreased open field activity scores in the High Pb group. In all cases, the behavioral response of the Pb exposed animals may be interpreted as responses characteristic of cholinergically deficient animals. These results thus provide further evidence for cholinergic system involvement in the behavioral changes observed following early exposure to Pb.