Synergism between cocaine and atropine at the caudal ventrolateral medullaof cats

We have previously reported that the anticholinergic properties of cocaine may be important in cocaine induced apneusis. We have studied the effects o f the cholinergic muscarinic antagonist atropine (ATR) on cocaine induced a pneusis at the caudal chemosensitive areas of the ventrolateral medulla obl ongata (CVLM). Experiments were performed in urethane anesthetized and trac heotomized cats with the CVLM surgically exposed. Topical application of AT R (44 mM) to the CVLM produced significant decrements in minute ventilation (V-F) and mean arterial blood pressure (MABP) (P <0.05) but the effects on tidal Volume (V-T), respiratory frequency (f) and heart rate (HR) were not significant. Administration of cocaine (37 mM) to ATR pretreated animals i ncreased the incidence of cocaine induced respiratory arrest to more than t wofold greater than when cocaine was administered in the absence of pretrea tment. The ATR pretreated animals that did not experience inspiratory arres t after cocaine were shown to exhibit significant decrements in f and V-E a s a consequence of prolonged inspiratory pauses. The reduction in MABP afte r cocaine in ATR pretreated animals was also significant. These results sug gest that ATR enhances the central respiratory toxicity of cocaine by actin g synergistically at CVLM chemosensitive sites. (C) 2001 Elsevier Science I nc. All rights reserved.