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 3.0 ppm 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 70.79 seconds, all 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; 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 exposure, the effects are reflected in the impact of reinforcing stimuli.

Effects of adolescent exposure to methylmercury and d-amphetamine on reversal learning and an extradimensional shift in male mice.

“…In both MeHg-exposure groups, the dose of MeHg was higher at the beginning of adolescence, and then tapered off to about 400 µg/kg/day. The pattern of dosing observed here is most likely due to a rapid rise in body mass coupled with a relatively stable level of water consumption throughout the adolescent period (Adriani, Macrì, Pacifici, & Laviola, 2002; Boomhower & Newland, 2016). Administration of d -AMP for two weeks (PND 28–42) during adolescence did not alter the dose of MeHg consumed relative to the MeHg-only group.…”

“…Exposure lasted from PND 21 through PND 59 (see Figure 1). A dose of 3 ppm MeHg was used because the daily dosing that it produces in mice results in permanent behavioral impairment without overt signs of toxicity in rats exposed during gestation (Paletz et al, 2007; Reed et al, 2006) or mice exposed during adolescence (Boomhower & Newland, 2016). …”

“…However, the long-term behavioral consequences of adolescent MeHg exposure have not been explored until recently (Boomhower & Newland, 2016). Adolescent MeHg exposure is especially concerning for a number of reasons.…”

An Information Theoretic Approach to Model Selection: A Tutorial with Monte Carlo Confirmation

“…From there, add 1 for each additional parameter being estimated. For example, in a study of the impact of adolescent exposure to the environmental contaminant methylmercury on adult behavior there was interest in which exposure level produced the major effects on delay discounting (Boomhower & Newland, 2016).…”

“…For example, 14 models of temporal discrimination were examined in humans in order to determine the role of clock speed in scaler expectancy theory and the behavior theory of timing (Beckmann & Young, 2009). In another example, the concatenated matching law formed the basis for describing the impact of methylmercury exposure on delay discounting in adults (Boomhower & Newland, 2016). Models were formed from different combinations of terms for magnitude sensitivity, delay sensitivity, dose, and whether individual mice were included as fixed or random effects.…”