THE EFFECT OF SELECTED CENTRAL NERVOUS SYSTEM DRUGS IN THE MORPHINE-TREATED RAT
Abstract
The opiate addict population has been reported to self-administer many drugs, most of which possess a strong central nervous system component (Chambers, 1969; Simpson and Sells, 1974; Clayton and Voss, 1981). This behavior increases the potential for adverse opiate-drug interactions. As previous behavioral studies in our laboratory have indicated possible morphine-drug interactions involving amphetamine, cocaine, diazepam, ethanol, and pentobarbital (Lesher, 1974; Wiechman, 1980; Schnur, 1981), current studies were designed in an attempt to characterize, biochemically, these interactions. Measurement of total morphine in plasma revealed no significant differences in any experimental group, although amphetamine, diazepam, pentobarbital and ethanol tended to increase levels of free morphine in the plasma of acute morphine-treated rats. Morphine-dependent rats administered ethanol displayed a decrese in unbound morphine when given ethanol. Cocaine increased brain morphine in acute morphine-treated rats, while ethanol decreased brain morphine levels in morphine-dependent rats. Brain:plasma total morphine ratios revealed amphetamine increased the ratio in acute morphine-treated rats while ethanol decreased the ratio. Morphine-dependent animals displayed a decreased ratio following either ethanol or diazepam administration. Glucocorticoid levels in naive rats given amphetamine, pentobarbital, and ethanol were lowered, while cocaine and diazepam raised these levels. All drugs exhibited an increase in glucocorticoid levels in morphine-dependent rats when compared with those treated acutely with morphine. Cocaine and diazepam decreased plasma glucocorticoid levels of acute morphine-treated rats when compared with saline, while ethanol increased the levels in such animals. Amphetamine and pentobarbital increased glucocorticoid levels in morphine-dependent animals when compared with shams. Dexamethasone pretreatment reduced the endogenous glucocorticoid levels in naive animals by approximately 50%. It was not capable of blocking the increases seen in the previous studies; in fact, dexamethasone treatment actually increased plasma glucocorticoid levels in some cases. Withdrawal studies revealed that only ethanol, by reducing both the number of wet dog shakes and the magnitude of weight loss, exhibited a consistent effect on morphine withdrawal. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of author.) UMI
Degree
Ph.D.
Subject Area
Pharmacology
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