Antidepressant effects on serotonin 1A/1B receptors in the rat brain using a gene x environment model

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• 作者：Stal Saurav Shrestha ; Daniel S. Pine ; David A. Luckenbaugh ; Katarina Varn盲s ; Ioline D. Henter ; Robert B. Innis ; Aleks ; er A. Math茅 ; Per Svenningsson
• 关键词：FSL/FRL (Flinders sensitive/resistant line) ; Serotonin 1A/1B (5-HT1A/1B) receptors ; Escitalopram ; Nortriptyline ; PFC (prefrontal cortex) ; Hippocampus ; Gene-environment (GxE)
• 刊名：Neuroscience Letters
• 出版年：24 January, 2014
• 年：2014
• 卷：559
• 期：Complete
• 页码：163-168
• 全文大小：1181 K

文摘

A gene-environment (GxE) interaction is implicated in both the pathophysiology and treatment of major depressive disorder (MDD). This study modeled the effects of genetic vulnerability by using the Flinders sensitive line (FSL), a rat model of depression and its control counterpart鈥攖he Flinders resistant line (FRL). The effects of environmental vulnerability (e.g., early-life stress) were modeled by using maternal separation. Rats (n = 105) were drawn from four groups reflecting experimental crossing of strain (FSL vs. FRL) and early-life stress (high vs. low) to assess the effects of two antidepressants (escitalopram or nortriptyline) compared to vehicle. Quantitative in vitro autoradiography was performed using [¹²⁵I]MPPI (5-HT_1A) and [¹²⁵I]CYP (5-HT_1B) in prefrontal cortex (PFC) and hippocampus. Stringent, Bonferroni-corrected statistical analyses showed significant strain-by-rearing-by-treatment (three-way) interactions in PFC 5-HT_1A and hippocampal 5-HT_1B receptors. Either vulnerability reduced serotonergic binding; no additive effects were associated with the two vulnerabilities. Both antidepressants increased hippocampal 5-HT_1B receptor binding; however, only nortriptyline selectively increased PFC 5-HT_1A receptor binding. Taken together, our findings demonstrate that antidepressant effects on the serotonergic system are shaped by a GxE interaction that depends on antidepressant class and brain region.