Responses of heart ornithine decarboxylase and adrenal catecholamines to methadone and sympathetic stimulants in developing and adults rats.

Sympathetic stimulation elevates heart ornithine decarboxylase (ODC) activity in adult rats, an effect which is followed by cardiac hypertrophy. In developing animals, adrenergic agonists play a role in cardiac growth and differentiation. Methadone administration to adult rats stimulated heart ODC, and this stimulation could be blocked by the sympatholytic agents chlorisondamine, reserpine or propranolol, suggesting that the effect is mediated via central stimulation of sympathetic nerves. With repeated methadone administration, tolerance developed to the heart ODC stimulation by methadone, eventually resulting in decreased heart ODC accompanied by deficits in heart weight. The sensitivity of the mature heart and adrenal medulla to the sympathetic stimulants insulin, nicotine or isoproterenol was virtually unchanged during long-term methadone administration, indicating that tolerance of the heart ODC response to methadone did not result from subsensitivity of the efferent sympathetic pathway or the heart ODC response system. In normally developing rats, responses to insulin-induced reflex stimulation of sympathetic nerve supplies to the heart and adrenal medulla did not occur until 8 days of postnatal age; however, daily treatment of pups with methadone begun the day after birth accelerated the development of functiona heart and adrenal medullary responses to insulin such that responses were obtained by 4 days of age. The cardiac responses to nicotine developed somewhat differently, with significant ODC stimulation first appearing at 12 days in controls and at 8 days in methadone-treated pups. In the adrenal gland, a tissue in which responses to nicotine do not depend on an intact nerve supply a catecholamine secretory response to nicotine was observed at 4 days of age in controls. These data suggest that methadone treatment accelerates the development of functional sympathetic innervation of heart and adrenal medulla, with resultant abnormalities in cardiac muscle growth and differentiation.