The opposite effect of a 5-HT_1B receptor agonist on 5-HT synthesis, as well as its resistant counterpart, in an animal model of depression

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• 作者：Ivan Skelin^a ; ^b ; Tomislav Kova膷evi膰^a ; ^c ; Hiroki Sato^a ; ¹ ; Mirko Diksic^a ; ^c ; ^{Mirko.diksic@mcgill.ca}
• 关键词：FSL ; Flinders Sensitive Line ; FRL ; Flinders Resistant Line ; 5-HT ; 5-hydroxytryptamine ; 伪-MTrp ; 伪-methyl-l-tryptophan ; CP-94253 ; 5-propoxy-3-(1 ; 2 ; 3 ; 6-tetrahydro-4-pyridinyl)-1H-pyrrolo [3 ; 2-b]pyridine hydrochloride ; DFP ; diisopropyl fluorophosphates
• 刊名：Brain Research Bulletin
• 出版年：2012
• 期刊代码：9_03619230
• 类别：neu
• 出版时间：1 August, 2012
• 卷：88
• 期：5
• 页码：477-486
• 文件大小：938 K

摘要

Flinders Sensitive Line (FSL) rat is as an animal model of depression with altered parameters of the serotonergic (5-HT) system function (5-HT synthesis rates, tissue concentrations, release, receptor density and affinity), as well as an altered sensitivity of these parameters to different 5-HT based antidepressants. The effects of acute and chronic treatments with the 5-HT_1B agonist, CP-94253 on 5-HT synthesis, in the FSL rats and the Flinders Resistant Line (FRL) controls were measured using 伪-[¹⁴C]methyl-l-tryptophan (伪-MTrp) autoradiography. CP-94253 (5 mg/kg), or an adequate volume of saline, was injected i.p. as a single dose in the acute experiment or delivered via the subcutaneously implanted osmotic minipump (5 mg/kg/day for 14 days) in the chronic experiment. The acute treatment with CP-94253 significantly decreased the 5-HT synthesis in both the FRL and FSL rats, with a more widespread effect in the FRL rats. Chronic treatment with CP-94253 significantly decreased 5-HT synthesis in the FRL rats, while 5-HT synthesis in the FSL rats was significantly increased throughout the brain. In both the acute and chronic experiment, the FRL rats had higher brain 5-HT synthesis rates, relative to the FSL rats.

The shift in the direction of the treatment effect from acute to chronic, using the 5-HT_1B agonist, CP-94253, on 5-HT synthesis in the FSL model of depression, with an opposite effect on the control FRL rats, suggests the differential adaptation of the 5-HT system in the FSL and FRL rats to chronic stimulation of 5-HT_1B receptors.