Methylmercury Exposure in Adolescence: Effects on Delay Discounting and Sensitivity to d-Amphetamine in Mice
Abstract
Methylmercury (MeHg) is an environmental neurotoxicant that can be used to study how cortical damage during early development affects behavior later in life. The consequences of MeHg exposure in adolescence, a developmental period in which the brain and behavior may be especially vulnerable to MeHg, is unknown. The current experiments were designed to assess the effects of low-level MeHg exposure during adolescence on delay discounting (i.e., preference for small, immediate reinforcers over large, delayed ones) and sensitivity to d-amphetamine (a dopamine agonist) using a mouse model. Thirty-six male C57BL/6n mice were exposed to 0, 0.3, or 3.0 ppm mercury (as MeHg) via drinking water from postnatal day 21 through 59, the murine adolescent period. As adults, mice lever-pressed for a 0.01-cc droplet of milk solution delivered immediately and four 0.01-cc droplets delivered after a series of delays for 35 sessions. A dose-response determination of d-amphetamine (i.p.; 0.1 – 1.7 mg/kg) followed. An information-theoretic analysis, which does not rely on traditional null-hypothesis testing, was employed to determine the most parsimonious model of the generalized matching equation to describe the data collected. Magnitude-sensitivity estimates were lower for mercury-exposed mice relative to controls, and delay-sensitivity estimates were reduced in the 0.3-ppm group compared to controls and the 3.0-ppm group. Further, d-amphetamine dose-dependently reduced delay-sensitivity estimates in all groups but decreased magnitude-sensitivity estimates only in the mercury-exposed groups. Adolescence is a developmental period during which the brain and behavior may be vulnerable to MeHg exposure.