Gordon-Fennell Adam G, Will Ryan G, Ramachandra Vorani, Gordon-Fennell Lydia, Dominguez Juan M, Zahm Daniel S, Marinelli Michela
Department of Neuroscience, College of Natural Sciences, The University of Texas at Austin, Austin, TX, United States.
Department of Psychology, College of Liberal Arts, The University of Texas at Austin, Austin, TX, United States.
Front Neurosci. 2020 Jan 17;13:1433. doi: 10.3389/fnins.2019.01433. eCollection 2019.
The lateral preoptic area (LPO) is a hypothalamic region whose function has been largely unexplored. Its direct and indirect projections to the ventral tegmental area (VTA) suggest that the LPO could modulate the activity of the VTA and the reward-related behaviors that the VTA underlies. We examined the role of the LPO on reward taking and seeking using operant self-administration of cocaine or sucrose. Rats were trained to self-administer cocaine or sucrose and then subjected to extinction, whereby responding was no longer reinforced. We tested if stimulating the LPO pharmacologically with bicuculline or chemogenetically with Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) modifies self-administration and/or seeking. In another set of experiments, we tested if manipulating the LPO influences cocaine self-administration during and after punishment. To examine the functional connectivity between the LPO and VTA, we used electrophysiology recordings in anesthetized rats. We tested if stimulating the LPO modifies the activity of GABA and dopamine neurons of the VTA. We found that stimulating the LPO reinstated cocaine and sucrose seeking behavior but had no effect on reward intake. Furthermore, both stimulating and inhibiting the LPO prevented the sustained reduction in cocaine intake seen after punishment. Finally, stimulating the LPO inhibited the activity of VTA GABA neurons while enhancing that of VTA dopamine neurons. These findings indicate that the LPO has the capacity to drive reward seeking, modulate sustained reductions in self-administration following punishment, and regulate the activity of VTA neurons. Taken together, these findings implicate the LPO as a previously overlooked member of the reward circuit.
外侧视前区（LPO）是下丘脑的一个区域，其功能在很大程度上尚未得到探索。它向腹侧被盖区（VTA）的直接和间接投射表明，LPO可能调节VTA的活动以及VTA所支持的与奖赏相关的行为。我们使用可卡因或蔗糖的操作性自我给药来研究LPO在奖赏获取和寻求中的作用。大鼠被训练自我给药可卡因或蔗糖，然后进行消退训练，即不再强化反应。我们测试了用荷包牡丹碱进行药理学刺激或用仅由设计药物激活的设计受体（DREADDs）进行化学遗传学刺激LPO是否会改变自我给药和/或寻求行为。在另一组实验中，我们测试了操纵LPO是否会影响惩罚期间和之后的可卡因自我给药。为了研究LPO和VTA之间的功能连接性，我们在麻醉的大鼠中进行了电生理记录。我们测试了刺激LPO是否会改变VTA中GABA和多巴胺神经元的活动。我们发现刺激LPO恢复了可卡因和蔗糖的寻求行为，但对奖赏摄取没有影响。此外，刺激和抑制LPO都阻止了惩罚后可卡因摄入量的持续减少。最后，刺激LPO抑制了VTA GABA神经元的活动，同时增强了VTA多巴胺神经元的活动。这些发现表明，LPO有能力驱动奖赏寻求，调节惩罚后自我给药的持续减少，并调节VTA神经元的活动。综上所述，这些发现表明LPO是奖赏回路中一个先前被忽视的成员。
