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Antidepressant effects on serotonin 1A/1B receptors in a rat model of depression with genetic and environmental vulnerabilities

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • S Shrestha
  • D Pine
  • D Luckenbaugh
  • K Varnas
  • I Henter
  • R Innis
  • A Mathe
  • P Svenningsson


Genes and early-life stress affect the incidence and expression of major depressive disorder (MDD) in humans. This study modeled the effects of genetic vulnerability by using the Flinders Sensitive Line (FSL), a rat model of depression, and the Flinders Resistant Line (FRL), its control counterpart. The effects of early-life stress were modeled by comparing normally reared and maternally separated rats. 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 antidepressant administration (either escitalopram or nortriptyline). Quantitative in vitro autoradiography was performed using two radioligands: [125I]MPPI (5-HT1A) in prefrontal cortex (PFC) and [125I]CYP (5-HT1B) in hippocampus. A stringent 3-WAY analysis showed a significant strain-by-rearing-by-treatment interaction in both PFC 5-HT1A and hippocampal 5-HT1B receptor density. Both the vulnerable strain factor (FSL) and the vulnerable environmental factor (early life stress) reduced both 5-HT1A and 5-HT1B receptor density in vehicle-exposed rats. In contrast, both antidepressants increased hippocampal 5-HT1B receptor density. Nortriptyline selectively increased PFC 5-HT1A receptor density. Taken together, the findings demonstrate that antidepressant effects on the serotonergic system are shaped by complex, gene-by-environment interactions.

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