engleski

Role of raphe 5-HT1A receptors in phrenic long-term depression in anesthetized rats

In experimental animals repeated bouts of hypercapnia may evoke sustained depression of phrenic nerve activity, known as phrenic long-term depression (pLTD). Serotonin (5-HT) has been shown to modulate respiratory neuronal activity, possibly via projections originating in the raphe nuclei. The present study was performed to investigate the role of 5-HT1A receptors in the caudal raphe region in pLTD development. Our hypothesis was that microinjections of selective 5-HT1A receptor agonist 8-OH-DPAT into the caudal raphe nucleus could modulate pLTD after exposure to acute intermittent hypercapnia (AIHc). Adult male urethane-anesthetized, vagotomized, paralyzed, and mechanically ventilated Sprague- Dawley rats were exposed to AIHc protocol. Experimental group of animals (n=7) received microinjections of 8-OH-DPAT (0.02 M, 20±5 nl) into the caudal raphe region (midline, 2.5 mm deep, 0.2 mm rostral to the obex) whereas control group (n=6) received microinjections of 0.9% saline (20±5 nl) into the same site. Peak phrenic nerve activity (pPNA), burst frequency (f), and respiratory rhythm parameters were analyzed at baseline (T0), during five hypercapnic episodes (THc1-5), as well as at 15 (T15), 30 (T30), and 60 (T60) minutes after the end of the last hypercapnic episode. Peak phrenic nerve activity one hour post-hypercapnia decreased to 56.5±16.1% compared to baseline (P=0.04) in control group, and to 62.7±10.0% in 8-OH-DPAT group (P=0.01). In group of animals that received microinjections of 8-OH-DPAT into the caudal raphe region prior to hypercapnic stimulation respiratory frequency decreased from 45.9±2.0 breaths/min at T0 to 37.0±3.8 at T60 (P=0.04). In the control group, respiratory frequency was 41.0±3.1 breaths/min at T0 and 43.0±5.1 breaths/min at T60 (P>0.05). These data suggest that pLTD elicited by exposure to intermittent hypercapnia is mediated via 5-HT1A receptors in the caudal raphe region, indicating that 5-HT receptor activation at supraspinal level is important for induction of pLTD.

long-term depression; raphe; serotonin; phrenic nerve; rats

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