Diurnal Variations in Natural and Drug Reward, Mesolimbic Tyrosine Hydroxylase, and Clock Gene Expression in the Male Rat
Diurnal Variations in Natural and Drug Reward, Mesolimbic Tyrosine Hydroxylase, and Clock Gene Expression in the Male Rat
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DOI：
10.1177/0748730409346657
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发表时间：
2009-12-01
影响因子：
3.5
通讯作者：
Lehman, Michael N.
中科院分区：
文献类型：
--
作者：
Webb, Ian C.;Baltazar, Ricardo M.;Lehman, Michael N.
昼夜节律系统对行为和生理的影响是普遍存在的，之前的证据表明昼夜节律对药物寻求行为和对滥用药物的反应进行调节。为了进一步表征奖励的每日节律并将这些观察扩展到自然强化物，通过条件位置偏好范式评估了性和全身性安非他明的奖励价值的昼夜变化。为了确定奖励节律性的潜在机制，对腹侧被盖区 (VTA) 和伏隔核 (NAcc) 的酪氨酸羟化酶 (TH) 和核心时钟蛋白（Period1 和 Bmal1）的水平进行了全天检查。在最初的训练期间，雄性大鼠的性表现昼夜变化，在从亮到暗的过渡附近达到最低点。对于交配和与安非他明相关的奖励来说，昼夜节律也很明显。然而，这些特定刺激的节律在时间模式上表现出差异，性奖励在午夜期间显示出峰值，安非他明奖励在深夜和中午显示出高点，在从亮到暗的过渡之前显示出最低点。急性苯丙胺给药的运动激活作用也存在昼夜变化，在深夜达到峰值。 Western blot 分析显示，Period] 和 Bmal1 蛋白水平在 NAcc 中是有节律的，但在 VTA 中则不然。相比之下，NAcc 和 VTA 中的 TH 蛋白水平都有节律，但峰值不同，NAcc 中的峰值与性奖励峰值一致，而 VTA 中的峰值与安非他明奖励峰值相关。因此，自然奖励和药物相关奖励似乎都以昼夜方式变化，但其峰值和最低水平的时间不同。奖赏节律和中脑边缘 TH 蛋白水平之间的相位关系表明，NAcc 中多巴胺释放能力的增加可能是性相关奖赏节律的基础，而安非他明相关奖赏发生在诱发 NAcc DA 释放的可能性相对较低的时候。
The impact of the circadian timing system upon behavior and physiology is pervasive, and previous evidence suggests a circadian modulation of drug-seeking behavior and responsiveness to drugs of abuse. To further characterize daily rhythms in reward and to extend these observations to natural reinforcers, diurnal variation in the rewarding value of sex and systemic amphetamine was assessed via the conditioned place preference paradigm. To identify potential mechanisms for rhythmicity in reward, levels of tyrosine hydroxylase (TH) and core clock proteins (Period1 and Bmal1) were examined across the day in the ventral tegmental area (VTA) and the nucleus accumbens (NAcc). During an initial training period, male rat sexual performance varied diurnally with a nadir near the light-to-dark transition. Diurnal rhythms also were evident for both mating and amphetamine-related reward. However, the rhythms for these particular stimuli exhibited differences in their pattern of timing, with sex reward showing a peak during the middark period and amphetamine reward exhibiting high points during the late night and midday with a nadir prior to the light-to-dark transition. A diurnal variation also was seen for the locomotor-activating effect of acute amphetamine administration with a peak during the late night. Western blot analyses revealed that Period] and Bmal1 protein levels were rhythmic in the NAcc but not in the VTA. By contrast, TH protein levels were rhythmic in both the NAcc and VTA, but the peaks differed with that in the NAcc coinciding with the peak of sex reward and that in the VTA associated with the peak in amphetamine reward. Thus, it appears that both natural and drug-related reward vary in a diurnal fashion but differ in the timing of their peak and nadir levels. The phase relationships between reward rhythms and mesolimbic TH protein levels suggest that an increased capacity for the release of dopamine in the NAcc may underlie the rhythms in sex-related reward, while amphetamine-related reward occurs at a time when the likelihood of evoked NAcc DA release is relatively low.