Paletz Elliott M, Craig-Schmidt Margaret C, Newland M Christopher
Department of Psychiatry, University of Wisconsin-Madison, 6001 Research Park Boulevard, Madison, WI 53719, USA.
Neurotoxicol Teratol. 2006 Jan-Feb;28(1):59-73. doi: 10.1016/j.ntt.2005.11.003. Epub 2006 Jan 18.
Fish in the diet is the major source of methylmercury (MeHg) exposure, but eating fish also provides important nutrients. Many fish species contain essential long chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), an omega-3 (or n-3) fatty acid, that is important for neural development and function. To examine interactions between MeHg and n-3 fatty acids, female Long-Evans rats were exposed, in utero, to 0, 0.5, or 5 ppm MeHg via drinking water, approximating exposures of 0, 40, and 400 mug/kg/day. They also received pre- and postnatal exposure to a diet containing either fish oil or coconut oil, creating a 2 (Diet)x3 (MeHg) full factorial design, with 6-8 rats per cell. The diets were high or marginal, respectively, in n-3 fatty acids but approximately equal in n-6 fatty acids. No exposure-related effects on developmental milestones or growth were noted. Behavior was evaluated using a series of rapidly increasing fixed ratio (FR) schedules of sucrose reinforcement; 1, 5, 25 and 75 lever presses were required for sucrose delivery, with three sessions provided at each requirement. This phase was followed by four sessions of a differential-reinforcement-of-low-rate-behavior (DRL) schedule, in which presses preceded by 10 s (or more) without a press were reinforced. Subsequently, several progressive ratio (PR) schedules that increased response requirements throughout a single session by a rate of 5%, 10%, or 20% were imposed. Rats exposed during gestation to MeHg had significantly higher response rates than controls under the large FR schedules, during the first session of DRL, and the PR 5% schedule, but neither fish oil nor coconut oil modified MeHg's effects. This finding is consistent with hypotheses that developmental MeHg exposure produced perseverative responding or altered the sensitivity of behavior to its reinforcing consequences and that certain reinforcement contingencies can unmask MeHg's effects.
饮食中的鱼类是甲基汞(MeHg)暴露的主要来源,但食用鱼类也能提供重要的营养物质。许多鱼类含有必需的长链多不饱和脂肪酸,尤其是二十二碳六烯酸(DHA),一种ω-3(或n-3)脂肪酸,对神经发育和功能很重要。为了研究甲基汞与n-3脂肪酸之间的相互作用,将雌性Long-Evans大鼠在子宫内通过饮用水暴露于0、0.5或5 ppm的甲基汞,近似于0、40和400微克/千克/天的暴露量。它们在出生前和出生后还接受了含鱼油或椰子油饮食的暴露,形成了一个2(饮食)×3(甲基汞)的全因子设计,每个单元格有6-8只大鼠。这些饮食中n-3脂肪酸含量分别较高或处于边缘水平,但n-6脂肪酸含量大致相等。未观察到与暴露相关的对发育里程碑或生长的影响。使用一系列快速增加的蔗糖强化固定比率(FR)时间表来评估行为;蔗糖递送需要1、5、25和75次杠杆按压,每个要求提供三个时段。此阶段之后是四个时段的低速率行为差异强化(DRL)时间表,其中在10秒(或更长时间)无按压之前的按压会得到强化。随后,实施了几个累进比率(PR)时间表,在单个时段内将反应要求以5%、10%或20%的速率增加。在大FR时间表下、DRL的第一个时段以及PR 5%时间表期间,孕期暴露于甲基汞的大鼠的反应率显著高于对照组,但鱼油和椰子油均未改变甲基汞的影响。这一发现与以下假设一致,即发育过程中暴露于甲基汞会产生固执反应或改变行为对其强化后果的敏感性,并且某些强化意外情况可以揭示甲基汞的影响。