Background
Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat anxiety and
depressive disorders. These agents may cause upper gastrointestinal (GI) symptoms
that lead to their discontinuation. We examined whether SSRIs modify physiologic GI
motor activities in freely moving rats.
Methods
The SSRIs fenfluramine, fluvoxamine, paroxetine, and fluoxetine were administered
to 24-hour food-deprived rats, and then GI motility was measured in conscious, freely
moving rats using a strain gauge force transducer method. Plasma acyl ghrelin levels
were determined by enzyme immunoassay.
Results
Plasma acyl ghrelin levels were analyzed in conjunction with fasted motor activities.
Acyl ghrelin was increased in association with the occurrence of Phase III–like contractions
of the migrating motor complex in the antrum and duodenum. SSRIs decreased acyl ghrelin
and changed Phase III–like contractions to fed-like motor activities. Both effects
were blocked by 5-HT2c, but not 5-HT1b, receptor antagonist. Neither melanocortin
4 nor the 3/4 receptor antagonists blocked this motor effect, although they restored
the anorexia induced by SSRIs. The improving effect on GI motility by 5-HT2c receptor
(5-HT2cR) antagonist disappeared after treatment with a growth-hormone secretagogue
receptor antagonist, whereas ghrelin or ghrelin-releasing drug such as TJ-43 changed
SSRI-induced fed-like motor activities to fasted activities.
Conclusions
SSRIs have inhibitory effects on acyl ghrelin and GI motor activities through 5-HT2cR.
Our study identifies the importance and divergence of central 5-HT2cR pathways that
regulate GI motor activities through ghrelin and feeding/energy metabolism via melanocortin
4 receptor signaling.
Key Words
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Article Info
Publication History
Published online: December 08, 2008
Accepted:
October 20,
2008
Received in revised form:
October 3,
2008
Received:
July 16,
2008
Identification
Copyright
© 2009 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
