An assessment of the influence of sex and genotype on morphine withdrawal in mice.
Item
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Title
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An assessment of the influence of sex and genotype on morphine withdrawal in mice.
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Identifier
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AAI3115280
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identifier
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3115280
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Creator
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Palmese, Christina A.
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Contributor
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Adviser: Benjamin Kest
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Date
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2004
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Language
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English
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Publisher
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City University of New York.
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Subject
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Psychology, Physiological | Biology, Neuroscience | Health Sciences, Pharmacology
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Abstract
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Several studies have examined the influence of sex and genotype on morphine withdrawal in animals, though a limited number of genotypes have been studied, acute withdrawal has not been assessed, and the data on sex differences are inconclusive. Using the jumping response as a measure of withdrawal, the first experiment generated morphine and naloxone dose-response curves for male and female CD-1 mice after acute and chronic morphine injection. To control for contextual learning and spontaneous withdrawal effects, mice of both sexes were also compared after continuous morphine infusion. Results showed that mean jumping frequencies were four-fold greater in males, who also displayed greater withdrawal sensitivity than females. In contrast, after chronic morphine injection, males and females displayed similar mean jumping frequencies and withdrawal sensitivity. Sex differences in withdrawal jumping were also absent when morphine treatment was administered by continuous infusion.;The second experiment assessed naloxone precipitated withdrawal jumping in male and female mice of 11 inbred strains (129P3, A, AKR, BALB/c, C3H/He, C57BL/6, CBA, DBA/2, LP, SJL, SWR) after acute and chronic injection, and continuous morphine infusion. There were differences in the magnitude of jumping between the three different morphine administration paradigms, and large and significant strain differences were observed for each. The 129P3, LP, A, and SJL strains displayed the least number of withdrawal jumping behaviors, the C57BL/6, AKR, and C3H/H3 strains were intermediately sensitive to withdrawal, and the DBA, CBA, and BALB/c strains were highly sensitive. The SWR strain displayed unusually high withdrawal sensitivity. Jumping means between acute and chronic paradigms displayed a high degree of genetic correlation ( r = 0.87--0.95).;The third study utilized a quantitative trait locus (QTL) mapping approach. The F2 generation of mice from progenitors of 129P3 and C57BL/6 inbred mouse strains were phenotyped and genotyped at 88 microsatellite markers. Sex differences were not observed in mice hetero- or homozygous at the D 1 Mit48 allele. There was a significant association between withdrawal jumping and a 28 cM-wide region of chromosome 1 (peak: 51 cM). The gene(s) in this region explain 25% of the phenotypic and 16% of the genotypic variance in this trait.
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Type
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dissertation
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Source
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PQT Legacy Restricted.xlsx
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degree
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Ph.D.