STUDIES ON THE RELATIONSHIP BETWEEN 5-HYDROXY-TRYPTAMINE TURNOVER IN BRAIN AND TOLERANCE AND PHYSICAL DEPENDENCE IN MICE

¹ Department of Pharmacology, University of Minnesota, College of Medical Sciences, Minneapolis, Minnesota

There is a gradual increase in the brain 5-hydroxytryptamine (5-HT) turnover rate over a three-day period after morphine pellet implantation in mice. p-Chlorophenylalanine (PCPA) given in conjunction with morphine injections partially suppresses not only the development of tolerance to morphine but also cross-tolerance development to several narcotic and narcotic antagonist analgesics. When the same mice are tested for physical dependence by the naloxone-induced jumping syndrome, PCPA fails to alter the incidence of jumping. In morphine-implanted mice, pargyline pretreatment before the naloxone challenge, greatly enhances the jumping syndrome. PCPA or reserpine given before and during morphine implantation does not decrease the incidence of naloxone-induced jumping. The brain 5-HT turnover between mice that jumped and the nonjumping mice does not differ. There appears to be no causal relation between brain 5-HT metabolism and physical dependence but some relation between tolerance and 5-HT turnover may exist.

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