INTERACTION OF D-LSD WITH BINDING SITES IN BRAIN: A STUDY IN VIVO AND IN VITRO (SEROTONIN, RADIOAUTOGRAPHY, HALLUCINOGEN).
Item
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Title
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INTERACTION OF D-LSD WITH BINDING SITES IN BRAIN: A STUDY IN VIVO AND IN VITRO (SEROTONIN, RADIOAUTOGRAPHY, HALLUCINOGEN).
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Identifier
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AAI8601635
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identifier
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8601635
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Creator
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EBERSOLE, BARBARA L. JONES.
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Contributor
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Harel Weinstein
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Date
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1985
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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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Health Sciences, Pharmacology
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Abstract
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The localization of ('3)H -d-lysergic acid diethylamide ( ('3)H LSD) binding sites in the mouse brain was compared in vivo and in vitro. Radioautography of brain sections incubated with ('3)H LSD in vitro revealed substantial specific ('3)H LSD binding in cortical layers III-IV and areas CA1 and dentate gyrus in hippocampus. In contrast, in brain sections from animals that received ('3)H LSD in vivo, binding in hippocampus was scant and diffuse, although the pattern of labeling in cortex was similar to that seen in vitro. The low specific binding in hippocampus relative to cortex was confirmed by homogenate filtration studies of brain areas from mice that received injections of ('3)H LSD. Time-course studies established that peak specific binding at ten minutes was the same in cortex and hippocampus. At all times, binding in hippocampus was about one-third of that in cortex; in contrast, the concentration of free ('3)H LSD did not vary between regions. This finding was unexpected, because binding studies in vitro in membrane preparations indicated that the density and affinity of ('3)H LSD binding sites were similar in both brain regions.;Saturation binding studies in vivo showed that the lower amount of ('3)H LSD binding in hippocampus was attributable to a lower density of sites labeled by ('3)H LSD. Competition binding studies in vivo with drugs selective for 5-HT(,1) and 5-HT(,2) serotonin binding sites showed that most of the sites labeled in vivo by ('3)H LSD were the 5-HT(,2) type; the 5-HT(,2) sites comprised about half of the ('3)H LSD binding in vitro in cortex, and about 10% of that in hippocampus in vitro. These findings suggest a hypothesis that explains the observed differences between ('3)H LSD binding in vivo and in vitro. In vivo, the 5-HT(,1) binding sites, which are putatively coupled to adenylate cyclase, bind agonists with low affinity in the presence of endogenous levels of guanine nucleotides, and thus the binding of ('3)H LSD as an agonist to these sites would not occur at the concentrations of ('3)H LSD attained in the studies in vivo. ('3)H LSD binding to 5-HT(,2) sites, however, does occur at these concentrations. The pharmacological identity of ('3)H LSD binding sites in vivo may be relevant to the hallucinogenic properties of LSD and of other related hallucinogens.
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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.
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Program
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Biomedical Sciences
