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

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Shrestha SS, Pine DS, Luckenbaugh DA, Varnas K, Henter ID, Innis RB, Mathe AA, Svenningsson P

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

Neurosci Lett. 2014 Jan 24;559:163-8. doi: 10.1016/j.neulet.2013.11.034. Epub 2013 Nov 25.

PubMed ID

24287374 [ View in PubMed

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Abstract

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-the 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 [(125)I]MPPI (5-HT1A) and [(125)I]CYP (5-HT1B) in prefrontal cortex (PFC) and hippocampus. Stringent, Bonferroni-corrected statistical analyses showed significant strain-by-rearing-by-treatment (three-way) interactions in PFC 5-HT1A and hippocampal 5-HT1B receptors. Either vulnerability reduced serotonergic binding; no additive effects were associated with the two vulnerabilities. Both antidepressants increased hippocampal 5-HT1B receptor binding; however, only nortriptyline selectively increased PFC 5-HT1A 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Nortriptyline	5-hydroxytryptamine receptor 1A	Protein	Humans	Unknown	Antagonist	Details