Contusion spinal cord injury (SCI) at T8 produces respiratory abnormalities in conscious rats breathing room air and challenged with CO 2 . In seeking ways to improve respiration after SCI, we tested drugs that stimulate serotonin 1A (5-HT 1A ) receptors, based on our previous findings that these agents can counteract respiratory depression produced by morphine overdose. Respiratory function was measured with a head-out plethysmograph system in conscious rats. T8 SCI rats (n ϭ 5) showed

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... d tidal volume (Vt; 0.90 Ϯ 0.02-0.66 Ϯ 0.03 ml; p Ͻ 0.05) and increased respiratory rate ( f; 91 Ϯ 3.7-132 Ϯ 5.7 breaths/min; p Ͻ 0.05) with room air ventilation at 24 hr after injury. They also exhibited a diminished response to the respiratory stimulating effect of 7% CO 2 ; minute ventilation increased to 250 Ϯ 17 ml/min before, but only to 162 Ϯ 15 ml/min at 24 hr after SCI ( p Ͻ 0.05). Respiratory deficits during room air ventilation were also observed at 7 d after injury (n ϭ 3). Treatment with the 5-HT 1A receptor agonist 8-hydroxy-2-(di-n-propylmino)tetralin (8-OH-DPAT; 250 g/kg, i.p.) at 24 hr (n ϭ 5) or 7 d (n ϭ 3) after injury normalized Vt, f, and the respiratory response to 7% CO 2 . Identical results were obtained with another 5-HT 1A receptor agonist, buspirone (1.5 mg/kg, i.p.; n ϭ 3). In contrast, intraperitoneal saline vehicle administration (n ϭ 5) showed no beneficial effects on SCI-impaired respiration. Finally, pretreatment with a specific antagonist of 5-HT 1A receptors, 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide (3 mg/kg, i.p.; n ϭ 3) given 20 min before 8-OH-DPAT, prevented 8-OH-DPAT from restoring respiration to normal. Our results demonstrate that drugs that stimulate 5-HT 1A receptors counteract respiratory abnormalities in conscious rats after SCI.