Adolescent methylmercury exposure affects choice and delay discounting in mice

Abstract

The developing fetus is vulnerable to low-level exposure to methylmercury (MeHg), an environmental neurotoxicant, but the consequences of exposure during the adolescent period remain virtually unknown. The current experiments were designed to assess the effects of low-level MeHg exposure during adolescence on delay discounting, preference for small, immediate reinforcers over large, delayed ones, using a mouse model. Thirty-six male C57BL/6n mice were exposed to 0, 0.3, or 3.0ppm mercury (as MeHg) via drinking water from postnatal day 21 through 59, encompassing the murine adolescent period. As adults, mice lever pressed for a 0.01-cc droplet of milk solution delivered immediately or four 0.01-cc droplets delivered after a delay. Delays ranged from 1.26 to 70.79s, and all were presented within a session. A model based on the Generalized Matching Law indicated that sensitivity to reinforcer magnitude was lower for MeHg-exposed mice relative to controls, indicating that responding in MeHg-exposed mice was relatively indifferent to the larger reinforcer. Sensitivity to reinforcer delay was reduced (delay discounting was decreased) in the 0.3-ppm group, but not in the 3.0-ppm group, compared to controls. Adolescence is a developmental period during which the brain and behavior may be vulnerable to MeHg exposure. As with gestational MeHg exposure, the effects are reflected in the impact of reinforcing stimuli.

Keywords: Adolescence; Delay discounting; Impulsive choice; Matching law; Methylmercury.

Figure 1

Left panels: Mean (±SD) dose of MeHg as a function of postnatal day for mice exposed to 0.3 (top) and 3.0 ppm MeHg (bottom) during the adolescent period (postnatal day 21 through 59). Doses were estimated by by averaging the intake of two pair-housed mice. Right panels: Mean (±SD) body mass and water consumption throughout adolescence. Note the y-axes in the left panels differ by an order of magnitude and all error bars represent one SD rather than one SEM.

Figure 2

Mean (+SD) total brain mercury at postnatal day (PND) 40, 59, and 90 for 0.3- and 3.0-ppm MeHg exposed mice. Total brain mercury in control animals was assessed at PND 59 only. Exposure lasted from PND 21 through 59. Note errors bars represent one SD rather than one SEM and are too small to visualize in some cases.

Figure 3

Log response ratio as a function of log delay ratio for individual mice. Each panel shows data from three littermates exposed to 0, 0.3, and 3.0 ppm MeHg during adolescence. Lines represent the best model of Eq. 1 according to the model-comparison analysis in which s_M (affecting the line's intercept) varied across all exposure groups, and s_D (affecting the line's slope) varied for 0.3 ppm MeHg-exposed mice and remained constant for both controls and 3.0 ppm MeHg-exposed mice. Log response and log delay ratios were calculated by dividing those of the larger-reinforcer lever (L) by the smaller (S).

Figure 4

Left panel: Mean (±SEM) proportion larger-reinforcer choice as a function of delay for MeHg-exposed mice. Right panel: Mean (±SEM) log response ratio as a function of log delay ratio for MeHg-exposed mice. All lines represent the mean predictions of Eq. 1 according to the best model.

Figure 5

Mean (±SEM) parameter estimates of magnitude (left) and delay sensitivity (right) for MeHg-exposed mice. The best model indicated s_M varied across all exposure groups, and s_D varied for only 0.3 ppm MeHg-exposed mice and remained constant for both controls and 3.0 ppm MeHg-exposed mice.