Fitzpatrick Christopher J, Creeden Justin F, Perrine Shane A, Morrow Jonathan D
Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan.
Department of Psychiatry, University of Michigan, Ann Arbor, Michigan.
Hippocampus. 2016 Nov;26(11):1424-1434. doi: 10.1002/hipo.22619. Epub 2016 Jul 30.
Individual variation in the attribution of motivational salience to reward-related cues is believed to underlie addiction vulnerability. Pavlovian conditioned approach measures individual variation in motivational salience by identifying rats that are attracted to and motivated by reward cues (sign-trackers) or motivationally fixed on the reward itself (goal-trackers). Previously, it has been demonstrated that sign-trackers are more vulnerable to addiction-like behavior. Moreover, sign-trackers release more dopamine in the nucleus accumbens than goal-trackers in response to reward-related cues, and sign- but not goal-tracking behavior is dopamine-dependent. In the present study, we investigated whether the ventral hippocampus, a potent driver of dopaminergic activity in the nucleus accumbens, modulates the acquisition and expression of Pavlovian conditioned approach behavior. In Experiment 1, lesions of the ventral, but not dorsal or total hippocampus, decreased sign-tracking behavior. In Experiment 2, lesions of the ventral hippocampus did not affect the expression of sign- or goal-tracking behaviors nor conditioned reinforcement. In addition, temporary inactivation of the ventral subiculum, the main output pathway of the ventral hippocampus, did not affect the expression of sign- or goal-tracking behaviors. High-pressure liquid chromatography of nucleus accumbens tissue punches revealed that ventral hippocampal lesions decreased levels of homovanillic acid and the homovanillic acid/dopamine ratio (a marker of dopamine release and metabolism) in only sign-trackers, and decreased accumbal norepinephrine levels in both sign- and goal-trackers. These results suggest that the ventral hippocampus is important for the acquisition but not expression of sign-tracking behavior, possibly as a result of altered dopamine and norepinephrine in the nucleus accumbens. © 2016 Wiley Periodicals, Inc.
动机显著性归因于奖励相关线索的个体差异被认为是成瘾易感性的基础。巴甫洛夫条件性趋近行为通过识别被奖励线索吸引并受其驱动的大鼠(信号追踪者)或动机固定于奖励本身的大鼠(目标追踪者)来测量动机显著性的个体差异。此前已经证明,信号追踪者更容易出现成瘾样行为。此外,与目标追踪者相比,信号追踪者在伏隔核中对奖励相关线索的反应会释放更多多巴胺,并且信号追踪行为而非目标追踪行为依赖多巴胺。在本研究中,我们调查了伏侧海马体(伏隔核多巴胺能活动的有力驱动者)是否调节巴甫洛夫条件性趋近行为的习得和表达。在实验1中,伏侧海马体而非背侧或整个海马体的损伤减少了信号追踪行为。在实验2中,伏侧海马体的损伤并未影响信号或目标追踪行为的表达以及条件性强化。此外,伏侧海马体的主要输出通路——伏侧下托的暂时失活并未影响信号或目标追踪行为的表达。对伏隔核组织切片进行的高压液相色谱分析显示,伏侧海马体损伤仅使信号追踪者的高香草酸水平及其与多巴胺的比值(多巴胺释放和代谢的标志物)降低,并且使信号追踪者和目标追踪者的伏隔核去甲肾上腺素水平均降低。这些结果表明,伏侧海马体对信号追踪行为的习得而非表达很重要,这可能是由于伏隔核中多巴胺和去甲肾上腺素的改变所致。© 2016威利期刊公司