A hypothesis about how early developmental methylmercury exposure disrupts behavior in adulthood

• Methylmercury disrupts brain development.
• Pregnant women are advised to avoid certain fish because of methylmercury.
• Developmental exposure causes behavioral deficits in adulthood and aging.
• Effects includes behavioral rigidity, disrupted reinforcement processing, and irreversible changes in sensitivity to GABAergic and dopaminergic drugs.
• It is hypothesized that enhanced impacts of reinforcers caused by early methylmercury exposure results in disrupted choice and perseveration.
• Methylmercury neurotoxicity may offer a model of abnormal brain development.

Events that disrupt the early development of the nervous system have lifelong, irreversible behavioral consequences. The environmental contaminant, methylmercury (MeHg), impairs neural development with effects that are manifested well into adulthood and even into aging. Noting the sensitivity of the developing brain to MeHg, the current review advances an argument that one outcome of early MeHg exposure is a distortion in the processing of reinforcing consequences that results in impaired choice, poor inhibition of prepotent responding, and perseveration on discrimination reversals (in the absence of alteration of extradimensional shifts). Neurochemical correlates include increased sensitivity to dopamine agonists and decreased sensitivity to gamma-aminobutyric acid (GABA) agonists. This leads to a hypothesis that the prefrontal cortex or dopamine neurotransmission is especially sensitive to even subtle gestational MeHg exposure and suggests that public health assessments of MeHg based on intellectual performance may underestimate the impact of MeHg in public health. Finally, those interested in modeling neural development may benefit from MeHg as an experimental model.