8-OH-DPAT abolishes the pulmonary C-fiber-mediated apneic response to fentanyl largely via acting on 5HT 1A receptors in the nucleus tractus solitarius

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2012-08, Vol.303 (4), p.R449-R458
• Main Authors: Zhuang, Jianguo, Zhang, Zhenxiong, Zhang, Cancan, Xu, Fadi
• Format: Article
• Language: English
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00016.2012

Intravenous bolus injection of morphine causes a vagal-mediated brief apnea (∼3 s), while continuous injection, via action upon central μ-opioid receptor (MOR), arrests ventilation (>20 s) that is eliminated by stimulating central 5-hydroxytryptamine 1A receptors (5HT 1A Rs). Bronchopulmonary C-fibers (PCFs) are essential for triggering a brief apnea, and their afferents terminate at the caudomedial region of the nucleus tractus solitarius (mNTS) that densely expresses 5HT 1A Rs. Thus we asked whether the vagal-mediated apneic response to MOR agonists was PCF dependent, and if so, whether this apnea was abolished by systemic administration of 8-hydroxy-2-(di- n-propylamino)tetral (8-OH-DPAT) largely through action upon mNTS 5HT 1A Rs. Right atrial bolus injection of fentanyl (5.0 μg/kg, a MOR agonist) was performed in the anesthetized and spontaneously breathing rats before and after: 1) selective blockade of PCFs' conduction and subsequent bivagotomy; 2) intravenous administration of 5HT 1A R agonist 8-OH-DPAT; 3) intra-mNTS injection of 8-OH-DPAT; and 4) intra-mNTS injection of 5HT 1A R antagonist WAY-100635 followed by 8-OH-DPAT (iv). We found the following: First, fentanyl evoked an immediate apnea (2.5 ± 0.4 s, ∼6-fold longer than the baseline expiratory duration, T E ), which was abolished by either blocking PCFs' conduction or bivagotomy. Second, this apnea was prevented by systemic 8-OH-DPAT challenge. Third, intra-mNTS injection of 8-OH-DPAT greatly attenuated the apnea by 64%. Finally, intra-mNTS microinjection of WAY-100635 significantly attenuated (58%) the apneic blockade by 8-OH-DPAT (iv). We conclude that the vagal-mediated apneic response to MOR activation depends on PCFs, which is fully antagonized by systemic 8-OH-DPAT challenge largely via acting on mNTS 5HT 1A Rs.