A COMPARATIVE STUDY IN THE CAT OF THE RESPIRATORY EFFECTS OF MORPHINE INJECTED INTRAVENOUSLY AND INTO THE CEREBROSPINAL FLUID

¹ Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire

Experiments were performed on cats anesthetized with Dial-urethane. Respiration was recorded plethysmographically and end-expiratory CO₂ was monitored continuously. Morphine sulfate was injected i.v. and through cannulas inserted stereotactically into the third and fourth ventricles and into the bulbar subarachnoid space. Morphine in the fourth ventricle and subarachnoid space (10-50 µg in 50 µl) induced respiratory depression qualitatively similar to that obtained after i.v. injection (1 mg/kg). Elevation in end-expiratory percent CO₂ was accounted for primarily by reduction of frequency. After i.v. injection, the beginning and peak effect of the depression appeared earlier than after injection into the fourth ventricle and subarachnoid space. Morphine was slightly more effective in the subarachnoid space than in the fourth ventricle. On the other hand, morphine in the third ventricle (50 µg in 50 µl) elicited an immediate respiratory stimulation followed by a second phase during which frequency remained elevated but tidal volume was progressively reduced and end-expiratory CO₂ was increased. Analysis of the relationship between CO₂ and tidal volume response data showed that the depressant effect of morphine by any of the appropriate routes was characterized by an elevation of the apneic point and reduction in slope above the resting level. Injection into the third ventricle then tended to restore the CO₂ response curves toward normal during the stimulation phase.

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