Maternal high fat diet during the perinatal period alters mesocorticolimbic dopamine in the adult rat offspring: reduction in the behavioral responses to repeated amphetamine administration
Maternal high fat diet during the perinatal period alters mesocorticolimbic dopamine in the adult rat offspring: reduction in the behavioral responses to repeated amphetamine administration
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DOI：
10.1007/s00213-007-1008-4
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发表时间：
2008-03-01
影响因子：
3.4
通讯作者：
Walker, Claire-Dominique
中科院分区：
文献类型：
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作者：
Naef, Lindsay;Srivastava, Lalit;Walker, Claire-Dominique
早期环境可以塑造中皮质边缘多巴胺（DA）系统的发育和功能，并代表成人病理学的一个可能的风险因素。早期环境中的一个关键变量是营养，并且已知成年期暴露于高脂肪（HF）会改变这种DA系统。目的我们测试大鼠围产期HF摄入是否会对成年后代的DA功能和行为产生长期影响。材料和方法在妊娠期和哺乳期的最后一周期间，测试了（5%脂肪，CD）或高脂肪（30%脂肪，HF）饮食，并在CD断奶后对成年后代进行了测试（PND 56-90）。急性和重复剂量D-苯丙胺的运动反应结果成年HF仔鼠腹侧被盖区（VTA）和前额叶皮层（PFC）的酪氨酸羟化酶表达增加，NAc的DA和DOPAC含量显著增加，表明这个靶区多巴胺水平升高在NAc中，饮食组之间的D1，D2受体或DA转运蛋白（DAT）水平没有显着变化。围产期HF喂养减少AMP诱导的运动和行为敏感AMP，这表明早期饮食可能会造成长期的突触后受体机制在NAc.Conclusions我们的研究结果表明，VTA神经元的合成活性和反应性的多巴胺神经元被改变母体营养。这些影响消退后很长一段时间终止暴露于HF饮食。
Rationale Early environment can shape the development and function of the mesocorticolimbic dopamine (DA) system and represents a possible risk factor for adult pathologies. One critical variable in the early environment is nutrition, and exposure to high fat (HF) in adulthood is known to change this DA system.Objectives We tested whether perinatal HF intake in rats could have long-term effects on DA function and behavior in adult offspring.Materials and methods Rat dams were fed either a control (5% fat, CD) or high fat (30% fat, HF) diet during the last week of gestation and lactation, and adult offspring were tested (PND 56-90) after weaning on CD. Locomotor responses to acute and repeated doses of D-amphetamine (AMP, 0.75 mg/kg bw) were determined as were indices of DA function in the ventral tegmental area (VTA), nucleus accumbens (NAc), and the prefrontal cortex (PFC).Results Adult HF offspring displayed increased tyrosine hydroxylase expression in the VTA and NAc and significant increases in DA and DOPAC content in the NAc, suggesting an elevated DA tone in this target field. In the NAc, there were no significant changes in D1, D2 receptors, or DA transporter (DAT) levels between diet groups. Perinatal HF feeding reduced AMP-induced locomotion and behavioral sensitization to AMP, suggesting that early diet might have caused long-lasting desensitization of postsynaptic receptor mechanisms in the NAc.Conclusions Our results demonstrate that both synthetic activity in VTA neurons and the responsiveness of accumbens DA neurons is altered by maternal nutrition. These effects subside long after termination of exposure to the HF diet.