5-HT4(a) receptors avert opioid-induced
breathing depression without loss of analgesia
by
Manzke T, Guenther U, Ponimaskin EG, Haller M,
Dutschmann M, Schwarzacher S, Richter DW.
Department of Neuro- and Sensory Physiology,
University of Goettingen, Humboldtallee 23,
37073 Goettingen, Germany.
Science. 2003 Jul 11;301(5630):226-9

ABSTRACT

Opiates are widely used analgesics in anesthesiology, but they have serious adverse effects such as depression of breathing. This is caused by direct inhibition of rhythm-generating respiratory neurons in the Pre-Boetzinger complex (PBC) of the brainstem. We report that serotonin 4(a) [5-HT4(a)] receptors are strongly expressed in respiratory PBC neurons and that their selective activation protects spontaneous respiratory activity. Treatment of rats with a 5-HT4 receptor-specific agonist overcame fentanyl-induced respiratory depression and reestablished stable respiratory rhythm without loss of fentanyl's analgesic effect. These findings imply the prospect of a fine-tuned recovery from opioid-induced respiratory depression, through adjustment of intracellular adenosine 3',5'-monophosphate levels through the convergent signaling pathways in neurons.

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