PET imaging of serotonergic transmission in monkeys: effects of maternal separation, and chronic fluoxetine treatment during adolescence

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NIMH	NEURO/BEHAV/SENSYS-21

* FARE Award Winner

Authors

• S Shrestha
• JS Liow
• R Gladding
• VW Pike
• PL Noble
• JT Winslow
• P Svenningsson
• SJ Suomi
• EE Nelson
• DS Pine
• RB Innis

Abstract

Major depressive disorder (MDD) is a serious disorder that often begins following stress during adolescence. SSRIs are common treatments for both adolescent and adult MDD. While MDD’s early onset and available efficacy data support use of SSRIs in adolescents, concerns about safety have arisen, based on associations with suicidal behavior in adolescents, coupled with minimal data on long-term effects on the developing brain. We used rhesus monkeys as a model to study the long term effects of both early life stress and chronic antidepressant treatment during adolescence (2-year of age) on the serotonin transporter (SERT) and 5-HT1A receptor. Thirty-two monkeys were randomly assigned to one of four groups (8 monkeys / group). One to two years post-washout, monkeys (average age of 5) were scanned with Positron Emission Tomography (PET) using [11C]DASB for SERT or [11C]RWAY for 5-HT1A receptor. Our data show 1. Significant two-way, rearing-by-treatment interactions emerged for SERT whereas only main effects for either rearing or treatment was seen for 5-HT1A receptors, and 2.Persistent effects of fluoxetine were seen on both markers. Our study demonstrates serotonergic alterations in PR monkeys, and chronic flouxetine treatment may reverse deficits in SERT density that is persistent > 1 year after medication discontinuation.

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