Faton Sina, Tassin Jean-Pol, Duranton Flore, Bagnol Didier, Lajoix Anne-Dominique
Department of CNS Drug Discovery, Arena Pharmaceuticals, Inc., San Diego, CA, USA; BioCommunication en Cardio-Métabolique, University of Montpellier, Montpellier, France.
Institut de Biologie Paris-Seine, Neuroscience, University Pierre and Marie Curie, Paris, France.
Behav Brain Res. 2018 Jul 16;347:234-241. doi: 10.1016/j.bbr.2018.03.006. Epub 2018 Mar 17.
Central serotonin systems have long been associated with the control of feeding behavior and the modulation of behavioral effects of psychostimulants. 5-HT receptors are present in hypothalamic centers such as the arcuate nucleus (ARC), controlling homeostatic regulation of food intake, as well as in the ventral tegmental area (VTA), a region involved in motivation aspects in multiple behaviors, including feeding. In the present study, we investigated whether the 5-HT receptors control amphetamine-evoked locomotor activity and regulate food consumption. Localized microinjections into the VTA or the ARC were used to assess the effects of a highly selective 5-HT receptor agonist, AR231630, on the locomotor stimulant effect of amphetamine as well as on food intake. AR231630 injected into the VTA, but not into the ARC, dose-dependently reduced locomotor activity elicited by amphetamine. Unexpectedly, intra-ARC injection of AR231630 did not reduce food intake even at the dose of 10 μg, whereas intra-VTA injection of the same dose of AR231630 did. In addition, we showed that pretreatment with the selective 5-HT receptor antagonist SB242084 infused into the VTA partially prevented hypophagia induced by peripheral administration of AR231630. We can conclude that 5-HT receptor in the VTA, but not in the ARC, participates in both homeostatic and hedonic food intake and brain reward function.
中枢5-羟色胺系统长期以来一直与进食行为的控制以及精神兴奋剂行为效应的调节有关。5-羟色胺受体存在于下丘脑中心，如弓状核（ARC），其控制食物摄入的稳态调节，同时也存在于腹侧被盖区（VTA），该区域参与包括进食在内的多种行为的动机方面。在本研究中，我们调查了5-羟色胺受体是否控制苯丙胺诱发的运动活动并调节食物消耗。通过向VTA或ARC进行局部微量注射，来评估高选择性5-羟色胺受体激动剂AR231630对苯丙胺的运动兴奋作用以及食物摄入的影响。注入VTA而非ARC的AR231630剂量依赖性地降低了苯丙胺诱发的运动活动。出乎意料的是，即使在10μg的剂量下，向ARC内注射AR231630也不会减少食物摄入量，而相同剂量的AR231630注入VTA则会减少食物摄入量。此外，我们还表明，向VTA注入选择性5-羟色胺受体拮抗剂SB242084进行预处理，可部分预防外周给予AR231630所诱导的摄食减少。我们可以得出结论，VTA而非ARC中的5-羟色胺受体参与了稳态和享乐性食物摄入以及脑奖赏功能。
