RESUMO
One of the complications of cocaine abuse is central cardiorespiratory failure. However, the site and mechanism of cocaine are unknown. The present study evaluates the effect of cocaine applied topically to the caudal and intermediate areas on the ventrolateral surface of the brainstem. These areas are known to be involved in the CO2 /pH chemosensory drive to respiration and in vasomotor control. Cats were anesthetized with urethane (2.0 g/kg), the trachea cannulated and the ventro-lateral surface of medulla oblongata (VMS) exposed. Cocaine prepared in mock CSF pH 7.4 was applied bilaterally to chemosensitive zones using pledgets. The effect of procaine was also tested. Tidal volume (Vt), respiratory frequency (f), arterial blood pressure (BP) and heart rate (HR) were monitored. Cocaine (62.5 ug/site) produced a significant decrease in minute ventilation (Ve) and blood pressure (BP) (p<0.05); the cuadal area was more sentive. In equimolar doses to cocaine, procaine (50 ug/site) produced small but significant effects on BP with no changes in Ve however, twice the equimolar dose(100 ug/site), produced respiratory responses similar to that of cocaine. Alpha and beta adrenoceptor antagonists prazosin (10 ug.site) and propranolol (16.7 ug/site) respectively, failed to alter the hypotensive or respiratory depressant effect of cocaine. Only animals that were hypotensive before or during physostigmine pretreatment (5 ug.site) experienced cardiorespiratory failure upon administration of cocaine. Carbachol (2.5 ug/site) had no effect on the cocaine induced cardiorespiratory responses. The present data suggest that (1) central cocaine neurotoxicity may result from interaction of cocaine with VMS sites; (2) the mechanism of action of cocaine at these sites is similar to that of procaine and does not appear to involve adrenergic receptors; and (3) pretreatment with the involve adrenergic receptors; and (3) pretreatment with the cholinomimetic physostigmine was effective in protecting animals from cocaine induced respiratory failure, its efficacy being limited to those animals that were not hypotensive during pretreatment. (AU)
