Central cocaine neurotoxicity at brainstem cardiorespiratory control sites.

Cocaine hydrochloride was applied topically to the ventrolateral medullary surface (VMS) where chemosensitive respiratory and vasomotor control sites are colocalized. Cats (n = 16) were anesthetized with urethane (2.0 g/kg, 80 percent of dose titrated over 60 min). The trachea of each animal was cannulated and the VMS was surgically exposed. Tidal volume (VT), frequency of breathing (f), systolic and diastolic blood pressure (SBP and DBP, respectively), and heart rate (HR) were measured. Cocaine (62.5 micrograms per site) administered at the VMS control sites decreased f, SBP, and DBP significantly (p < 0.05), without changing HR or VT values. This cocaine-induced hypoventilation was associated with brief intervals of inspiratory cramp (apneusis). Central cocaine neurotoxicity may result from interaction of cocaine with VMS sites, producing increased inspiratory drive and decreased vasomotor tone.