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Abstract

Characterization and autoradiographic localization of the cannabinoid binding site in rat brain using [3H]11-OH-delta 9-THC-DMH.

B F Thomas, X Wei and B R Martin
Journal of Pharmacology and Experimental Therapeutics December 1992, 263 (3) 1383-1390;
B F Thomas
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X Wei
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B R Martin
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Abstract

The binding of [3H]11-OH-delta 9-tetrahydrocannabinol-1, 1-dimethyl-heptyl (THC-DMH), a recently synthesized cannabinoid analog, was characterized in an in vitro brain slice binding assay and compared to that obtained with [3H]CP-55,940, the radiolabeled ligand used originally to characterize cannabinoid binding sites. The binding of both [3H]CP-55,940 and [3H]11-OH-delta 9-THC-DMH exhibited high affinity (Kd of 19 +/- 3 and 29 +/- 9 nM, respectively), and was saturable, reversible and specific. Values of maximal concentration of receptors determined for [3H]11-OH-delta 9-THC-DMH and [3H]CP-55,940 were 4.0 +/- 0.3 and 3.0 +/- 0.5 pmol/mg of protein, respectively. The distribution of [3H]11-OH-delta 9-THC-DMH and [3H]CP-55,940 binding in 30-microns rat brain sections was then compared by autoradiographic analysis. The binding of both ligands was densest in the basal ganglia (substantia nigra pars reticulata, globus pallidus, entopeduncular nucleus and regions of the caudate putamen) and cerebellum (molecular layer). Low levels of binding were observed in discrete brain regions including the brain stem (medulla and pons), thalamic nuclei, hypothalamus, corpus callosum and the deep nuclear layer of the cerebellum. Intermediate levels of binding were seen in layers I and VI of the cortex, and the dentate gyrus and CA pyramidal cell regions of the hippocampus. The ability of selected cannabinoid analogs to compete with [3H]11-OH-delta 9-THC-DMH binding was determined. The Ki's were correlated to the in vivo potencies for producing catalepsy, antinociception, hypothermia and decreasing spontaneous locomotor activity in mice (correlation coefficients > 0.86).(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 263, Issue 3
1 Dec 1992
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Abstract

Characterization and autoradiographic localization of the cannabinoid binding site in rat brain using [3H]11-OH-delta 9-THC-DMH.

B F Thomas, X Wei and B R Martin
Journal of Pharmacology and Experimental Therapeutics December 1, 1992, 263 (3) 1383-1390;

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Abstract

Characterization and autoradiographic localization of the cannabinoid binding site in rat brain using [3H]11-OH-delta 9-THC-DMH.

B F Thomas, X Wei and B R Martin
Journal of Pharmacology and Experimental Therapeutics December 1, 1992, 263 (3) 1383-1390;
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