Early-life low-level lead exposure alters anxiety-like behavior, voluntary alcohol consumption and AC5 protein content in adult male and female C57BL/6 J mice.

ABSTRACT

Despite efforts to eradicate sources of environmental lead (Pb), children, predominately in lower socioeconomic areas, are still frequently exposed to unsafe levels of Pb from soils, dust, and water. Human studies suggest that Pb exposure is associated with altered drug consumption in adults; however, there is limited research at comparable exposure levels (blood Pb levels <10 µg/dL). To model how early-life, low-level Pb exposure affects alcohol consumption in adulthood, we exposed postnatal day (PND) 21 C57Bl/6 J mice to either 30 ppm or 0 ppm Lead (IV) Acetate in distilled water until PND 42, and testing began in adulthood. We predicted that mice with early-life Pb exposure would exhibit greater anxiety-like behavior and consume more alcohol in a three-week Drinking-in-the-Dark procedure (20% v/v) and a 24-h two-bottle choice procedure (10% v/v). We also predicted that Pb exposure would decrease whole-brain content of Adenylate Cyclase-5 (AC5), a protein linked to anxiety-like behaviors and alcohol drinking. There was no difference in limited-access binge-like consumption between exposure groups; however, Pb-exposed mice displayed higher two-bottle choice alcohol intake and preference. Furthermore, Pb-exposed mice exhibited greater anxiety-like behaviors in experiments conducted before an alcohol drinking history but not after. Finally, Pb-exposed mice exhibited an upregulation of whole-brain AC5 protein content. However, this difference was not found in the nucleus accumbens, dorsomedial or dorsolateral striatum. These findings conclude that early-life Pb exposure alters voluntary alcohol consumption and whole-brain AC5 protein content in adulthood. Future studies are necessary to further understand the mechanism behind how Pb exposure alters alcohol intake.