Journal Article•
Brain serotonin turnover in morphine tolerant and dependent mice
01 Nov 1970-Journal of Pharmacology and Experimental Therapeutics (American Society for Pharmacology and Experimental Therapeutics)-Vol. 175, Iss: 2, pp 427-434
TL;DR: The results suggest that increased brain 5-HT synthesis may be associated with tolerance and physical dependence development to morphine in the mouse but do not establish a causal relationship.
Abstract: The rate of serotonin (5-HT) synthesis in the brains of mice rendered tolerant to and physically dependent on morphine either by s.c. implantation of a morphine pellet for three to four days or by daily s.c. injections of increasing doses of morphine was found to be about twice that of control animals receiving a placebo implant or daily saline injections. Inhibition of brain 5-HT synthesis by p -chlorophenylalanine was accompanied by a decrease in tolerance and dependence development to morphine. The concomitant administration of naloxone to reduce tolerance and physical dependence development to daily injections of morphine resulted also in a decrease in the rate of brain 5-HT synthesis. Although the roles of other biogenic amines have not been excluded, the results suggest that increased brain 5-HT synthesis may be associated with tolerance and physical dependence development to morphine in the mouse but do not establish a causal relationship.
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TL;DR: The results of these experiments indicate that drugs which specifically inhibit serotonin reuptake are capable of decreasing voluntary ethanol consumption, and the behavioral mechanism through which these drugs exert their effects seems to be extinction of the primary reinforcing properties of alcohol.
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TL;DR: It is suggested that the implantation of four morphine pellets in the rat produces a mild degree of dependence and that caution should be exercised when making generalized conclusions about the biochemical correlations involved when four or less number of pellets, each containing 75 mg of morphine base, are used to induce morphine dependence in the rats.
Abstract: Four schedules of subcutaneous morphine pellet implantation were developed to render rats rapidly physically dependent on morphine. The schedules included implantation of four morphine pellets over a 3-day period (schedule 1), six morphine pellets over a 3-day period (schedule 2), six pellets over a 7-day period (schedule 3), and ten pellets over a 10-day period (schedule 4). Each morphine pellet contained 75 mg of morphine base. The degree of morphine dependence was quantitated by determining the median effective dose (ED50) of naloxone required to induce the stereotyped jumping response. Hypothermia and weight loss, during abrupt and naloxone-induced withdrawal, were also measured. Rats on schedule 4 exhibited a high degree of dependence on morphine as evidenced by an extremely low naloxone ED50 for the precipitated withdrawal jumping response, whereas schedules 1 and 2 produced a low degree of dependence as shown by high naloxone ED50's. Further evidence for a high degree of physical dependence on morphine is schedule 4 rats was indicated by their greater loss in body weight and greater hypothermic response after abrupt and after naloxone precipitated withdrawal compared with these responses in the rats in the other three schedules. A correlation was found to exist between naloxone ED50 for the jumping response, body weight loss, and hypothermia observed during naloxone-induced withdrawal in morphine-dependent rats. These studies suggest that the implantation of four morphine pellets in the rat produces a mild degree of dependence and that caution should be exercised when making generalized conclusions about the biochemical correlations involved when four or less number of pellets, each containing 75 mg of morphine base, are used to induce morphine dependence in the rat.
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01 Jan 1977
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Abstract: Kenneth Blum, Murray G. Hamilton and J.E. Wallace The University of Texas Health Science Center at San Antonio, Departments of Pharmacology and Pathology, San Antonio, Texas, 78284, and The University of Western Ontario, Department of Pharmacology, London, Ontario, Canada. INTRODUCTI ON Among drugs of abuse, none have achieved such wide popularity as ethanol and opiate derivatives. Although these drugs are consumed by a large segment of our population, many consequences of acute and chronic intoxication with alcohol and opiates are not readily understood.
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Cites background or result from "Brain serotonin turnover in morphin..."
...(50) proposed that 5-HT may be associated with moprhine abstinence since PCPA and 5,6-dihydroxytryptamine inhibited wet-dog shakes following naloxone administration to tolerant-dependent morphine animals....
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...(50) reported that PCPA, which inhibits tryptophan-5-hydroxylase and thereby the synthesis of 5-HT, antagonized withdrawal symptomatology in mice....
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...The results obtained during withdrawal from opiates or ethanol are similarly contradictory with increases (37), decreases (37,49), and no effect on 5-HT concentrations (23,44,49,50)....
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