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Abstract
<p class="first" id="P2">Serotonin (5-HT) neurons are strongly implicated in mood
disorders such as depression
and are importantly regulated by feedback inhibition mediated by 5-HT
<sub>1A</sub> receptors. These receptors may play a role, albeit a poorly understood
one, in the
generation of mood disorders, treatment response to antidepressants and delayed therapeutic
efficacy. Here we sought to gain insight into the role of 5-HT
<sub>1A</sub> receptor-mediated feedback inhibition in these processes by studying
Fos protein
expression within serotonin neurons in a rat model of stress-related mood disorder,
early life maternal separation (MS), combined with two-week treatment with the antidepressant
fluoxetine (FLX) in adulthood. We gauged 5-HT
<sub>1A</sub> receptor-mediated feedback inhibition by the ability of the antagonist,
WAY-100635
(WAY), to disinhibit Fos expression in 5HT neurons. We found that two-week FLX treatment
dramatically inhibited Fos expression in serotonin neurons and that this effect was
reversed by blocking 5-HT
<sub>1A</sub> receptors with WAY. Together these observations reveal that after prolonged
exposure
to SSRIs, endogenous 5HT
<sub>1A</sub> receptors continue to exert feedback inhibition of serotonin neurons.
Furthermore
we found unique effects of pharmacological treatments after MS in that the WAY effect
was greatest in MS rats treated with FLX, a phenomenon selective to the rostral 2/3
of the dorsal raphe nucleus (B7). These results indicate that the balance between
activation and feedback inhibition of serotonin neurons in B7 is altered and uniquely
sensitive to FLX after early-life stress.
</p>