HISTOPATHOLOGICAL EVALUATION OF COCAINE-INDUCED SKIN-LESIONS IN THE RAT

A series of experiments was performed to characterize the nature of local tissue reactions to cocaine. The time-course of tissue injury was assessed over a 21-day period by gross and microscopic examination of the skin of rats administered 0.1-2.0% cocaine hydrochloride by i.c. [intracutaneous] or s.c. injection. Pronounced blanching, progressively severe hemorrhage, delayed extravasation of Evans blue dye, and eventual scar formation were seen grossly at injection sites. Marked engorgement of blood vessels, small hemorrhagic foci and hyalinization of scattered muscle bundles of the panniculus carnosus were apparent microscopically at 15 min postinjection. Subsequent changes during the next 3 h included progressively severe hemorrhage and loss of muscle bundles, degeneration of hair follicles and necrosis of the vascular endothelium and epidermis. Healing of cocaine-induced lesions, as monitored for 21 days, was relatively rapid and complete. A hyperplastic epidermis covered formerly ulcerated areas by 6 days. Destroyed cellular structures in the dermis were replaced by collagen. Since cocaine''s local tissue toxicity is ascribed to vasoconstriction, the toxic potential of cocaine was contrasted with that of a potent vasoconstrictor, epinephrine (EPI). Although 0.1% EPI produced greater vasoconstriction than did cocaine, s.c. EPI injection did not result in skin damage. The slight acidity of cocaine hydrochloride solutions appeared to be of little consequence, since s.c. injection of pH 5 and 6 saline had little effect on tissues. Evidently, cocaine is directly cytotoxic, though ischemia resulting from vascular injury and vasoconstriction may contribute to the local tissue injury caused by the drug.