Rea M A, Glass J D, Colwell C S
Circadian Neurobiology Research Group, Armstrong Laboratory, Brooks AFB, Texas 78235.
J Neurosci. 1994 Jun;14(6):3635-42. doi: 10.1523/JNEUROSCI.14-06-03635.1994.
The aim of the present study was to examine the effects of serotonin agonists on three elements of the photic response in the hamster suprachiasmatic nuclei (SCN). Both serotonin and the selective 5-HT1A agonist 8-OH-DPAT inhibited field potentials recorded in the SCN in response to optic nerve stimulation in the hypothalamic slice preparation. The effects of both drugs were dose related over a concentration range of 1-50 microM, and, in both cases, a maximal inhibition of approximately 60% was achieved at a concentration of 25-50 microM. Systemic administration of 8-OH-DPAT inhibited light-stimulated Fos expression in the SCN. A regionally selective pattern of inhibition was observed, with decreases restricted predominately to the ventral and dorsal borders of the SCN. Finally, systemic administration of 8-OH-DPAT was found to dose-dependently attenuate light-induced phase shifts of the free-running activity rhythm. The effects of 8-OH-DPAT on light-induced phase advances were dose dependent. Injection of 8-OH-DPAT at a dose of 0.5 mg/kg caused 57% inhibition of light-induced phase advances, while a dose of 5 mg/kg inhibited the phase advance by 82%. Injection of 0.05 mg/kg 8-OH-DPAT did not significantly inhibit light-induced phase advances. Injection of 5 mg/kg 8-OH-DPAT alone did not significantly alter the phase of the activity rhythm. Similarly, injection of 5 mg/kg 8-OH-DPAT 30 min prior to light stimulation at CT14 completely inhibited light-induced phase delays, while this dose of the drug did not alter the phase of the activity rhythm when administered alone.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究的目的是检验血清素激动剂对仓鼠视交叉上核(SCN)光反应三个要素的影响。血清素和选择性5-HT1A激动剂8-OH-DPAT均抑制下丘脑切片制备中SCN记录到的对视神经刺激的场电位。在1-50微摩尔的浓度范围内,两种药物的作用均与剂量相关,且在两种情况下,浓度为25-50微摩尔时均达到约60%的最大抑制率。全身性给予8-OH-DPAT可抑制SCN中光刺激诱导的Fos表达。观察到一种区域选择性抑制模式,抑制主要局限于SCN的腹侧和背侧边界。最后,发现全身性给予8-OH-DPAT可剂量依赖性地减弱自由活动节律的光诱导相移。8-OH-DPAT对光诱导的相位提前的作用具有剂量依赖性。以0.5毫克/千克的剂量注射8-OH-DPAT可导致光诱导相位提前受到57%的抑制,而5毫克/千克的剂量可将相位提前抑制82%。注射0.05毫克/千克的8-OH-DPAT并未显著抑制光诱导的相位提前。单独注射5毫克/千克的8-OH-DPAT并未显著改变活动节律的相位。同样,在CT14光照刺激前30分钟注射5毫克/千克的8-OH-DPAT可完全抑制光诱导的相位延迟,而单独给予该剂量的药物时并未改变活动节律的相位。(摘要截选至250字)