Penev P D, Turek F W, Zee P C
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208.
Brain Res. 1995 Jan 16;669(2):207-16. doi: 10.1016/0006-8993(94)01237-c.
Several lines of evidence suggest the potential involvement of serotonergic pathways in mediating the effects of activity-inducing stimuli on the circadian clock in rodents. The aim of the present 3 experiments was to examine the effects of the serotonergic neurotoxin, p-chloroamphetamine (PCA, 10 mg/kg) on: (1) the monoamine levels of the hypothalamus, frontal cortex and hippocampus in the hamster; (2) the phase shifts in the circadian rhythm of locomotor activity of hamsters in response to treatment with the short-acting benzodiazepine, triazolam (7.5 mg/kg); and (3) the magnitude of the acute increase in locomotor activity associated with triazolam administration in this species. The administration of PCA to hamsters caused changes of specific monoaminergic systems in the hypothalamus, that were limited to a selective decrease in serotonin levels 7 days post-treatment. The phase shifts of the circadian clock in response to triazolam treatment at CT 6 were considerably attenuated following the administration of the 5-HT neurotoxin. The total amount and the profiles of triazolam-induced wheel-running and general cage activity between CT 6 and CT 12 were not significantly affected by the PCA treatment. The finding that a 5-HT neurotoxin can attenuate the phase-shifting effects of triazolam in hamsters, without interfering with its activity-inducing properties, suggests that serotonergic afferents might be involved in the mechanism for non-photic phase-shifting of the circadian system.
多项证据表明,血清素能通路可能参与介导活动诱导刺激对啮齿动物昼夜节律钟的影响。本实验的目的是研究血清素能神经毒素对氯苯丙胺(PCA,10毫克/千克)对以下方面的影响:(1)仓鼠下丘脑、额叶皮质和海马体中的单胺水平;(2)短效苯二氮䓬类药物三唑仑(7.5毫克/千克)处理后仓鼠运动活动昼夜节律的相移;(3)该物种中与三唑仑给药相关的运动活动急性增加的幅度。给仓鼠注射PCA会导致下丘脑中特定单胺能系统发生变化,这种变化仅限于治疗后7天血清素水平的选择性降低。在注射5-羟色胺神经毒素后,在CT 6时对三唑仑治疗的昼夜节律钟相移明显减弱。PCA处理对CT 6和CT 12之间三唑仑诱导的转轮运动和一般笼内活动的总量和模式没有显著影响。5-羟色胺神经毒素可以减弱三唑仑对仓鼠的相移作用,而不干扰其诱导活动的特性,这一发现表明血清素能传入神经可能参与了昼夜节律系统非光性相移的机制。