EFFECTS OF CHOLINOMIMETICS ON COCAINE-INDUCED HYPOTENSION AND APNEUSIS AT A VENTRAL BRAIN-STEM CARDIORESPIRATORY CONTROL SITE

The current study was undertaken to evaluate the effects of cholinomim etic drugs on cocaine-induced central cardiorespiratory depression. Ca ts anesthetized by urethane (2.0 g/kg) were subjected to topical appli cation at the caudal ventrolateral medullary surface (cVMS) of cocaine and two cholinomimetic pretreatment drugs. The following drug regimen s were tested: 37 mM cocaine 1) given alone; 2) given 5 min after 2.7 mM carbachol pretreatment; and 3) given 5 min after 3.6 mM physostigmi ne pretreatment. In 7 of 11 cats, pretreatment with physostigmine decr eased the incidence of cocaine-induced apneusis and hypoventilation si gnificantly (p < 0.05); these animals showed no significant change in the mean arterial blood pressure during the 5-min pretreatment before administration of cocaine. In 4 of 11 cats, the physostigmine pretreat ment produced a significant decrease in mean arterial blood pressure f ollowed by lethal cardiorespiratory arrest when cocaine was administer ed. Pretreatment with carbachol resulted in cardiorespiratory response s which were not significantly different from those produced by cocain e alone. In anesthetized cats not exhibiting hypotensive responses to physostigmine, pretreatment may ameliorate cocaine-induced respiratory failure by ventral brainstem control mechanisms.