The behavioral and genetic determinants of anxiety as measured by the effects of antianxiety agents in mice.
Item
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Title
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The behavioral and genetic determinants of anxiety as measured by the effects of antianxiety agents in mice.
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Identifier
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AAI8914744
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identifier
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8914744
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Creator
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Builione, Robert Scott.
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Contributor
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Adviser: Solomon Steiner
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Date
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1988
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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, Clinical | Psychology, Experimental | Psychology, Physiological
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Abstract
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A novel behavioral model was established to test the anxiolytic effects of chlordiazepoxide in HS/IBg mice which may be functionally divided into two subgroups: resistant to the sedative effects of the anxiolytic diazepam (DR, drug resistant) and sensitive to the effects of diazepam (DS, drug sensitive). This new conflict model offers a major advantage over the older paradigms, i.e., a baseline is generated, using consummatory behavior as an operant, which is stable and permits each animal to serve as its own control. This model is, therefore, ideally suited for testing conflict behavior in a small animal population.;A dose of 11.41 mg/kg was necessary to increase DR responding 100% over baseline while doses of 5.57 and 5.87 mg/kg induced the same percent increase in control and DS mice, respectively. These results suggest a genetic pre-selection for resistancy toward the anxiolytic properties of the benzodiazepines (BDZ). These results can be explained by a resistance to the sedative properties of BDZ in DR mice as compared to DS and control animals. These data, however, do not support a behavioral difference between the sensitive and control sample. Behavioral data was also collected on the effects of chlordiazepoxide in potentiating the sedative effects (sleep time) of ethanol, across the DR and DS strains. The sleep times, induced by 3 g/kg ethanol were not significantly different when compared across strains (DR = 45.1 min., DS = 45.5 min.) At 10 mg/kg chlordiazepoxide, the DR mice slept, a significantly shorter time (81.4 min.) than either the control (127.5 min.) or sensitive (121.6 min.) strain.;Examination of the BDZ receptor biochemical pharmacology in the DR and DS cortical tissue did not demonstrate significant variation in K{dollar}\sb{lcub}\rm d{rcub}{dollar} or B{dollar}\sb{lcub}\rm max{rcub}{dollar} values. The K{dollar}\sb{lcub}\rm d{rcub}{dollar} values for the DR and DS strains were 0.96 and 0.95 nM, respectively. The B{dollar}\sb{lcub}\rm max{rcub}{dollar} values for the DR and DS strains were 1579.6 and 1587.8 fmoles/mg protein. Significant differences were noted in the K{dollar}\sb{lcub}\rm d{rcub}{dollar} values obtained in cerebellar tissue samples (DR = 2.06 nM, DS = 1.54 nM). While cortical, cerebellar and hippocampal samples all demonstrated increased affinity (K{dollar}\sb{lcub}\rm d{rcub}{dollar}) in the presence of GABA, no significant differences were evident across strain. Finally, ({dollar}\sp{lcub}35{rcub}{dollar}S) TBPS binding was evaluated as a biochemical measure of chloride channel function (Skolnick et al., 1986). Statistical analysis (A-L-Q analysis) of cortical samples indicated a trend toward a significant difference between the DR (213.6 cpm) and DS (194.4 cpm) lines.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
