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Journal of Neuroscience, Vol 6, 1757-1770, Copyright © 1986 by Society for Neuroscience
Autoradiographic localization of sigma receptor binding sites in guinea pig and rat central nervous system with (+)3H-3-(3-hydroxyphenyl)-N-(1- propyl)piperidine
AL Gundlach, BL Largent and SH Snyder
(+)3H-3-PPP [(+)3H-3-(3-Hydroxyphenyl)-N-(1-propyl)-piperidine] binds with
high affinity to brain membranes with a pharmacological profile consistent
with that of sigma receptors. The distribution of (+)3H-3- PPP binding
sites in brain and spinal cord of both guinea pig and rat has been
determined by in vitro autoradiography with binding densities quantitated
by computer-assisted densitometry. (+)3H-3-PPP binding to slide-mounted
brain sections is saturable and displays high affinity and a
pharmacological specificity very similar to sites labeled in homogenates.
(+)3H-3-PPP binding sites are heterogeneously distributed. Highest
concentrations of binding sites occur in spinal cord, particularly the
ventral horn and dorsal root ganglia; the pons- medulla, associated with
the cranial nerve and pontine nuclei and throughout the brain stem
reticular formation; the cerebellum, over the Purkinje cell layer; the
midbrain, particularly the central gray and red nucleus; and hippocampus,
over the pyramidal cell layer. Lowest levels are seen in the basal ganglia
and parts of the thalamus, while all other areas, including hypothalamus
and cerebral cortex, exhibit moderate grain densities. Quinolinic
acid-induced lesions of the hippocampus indicate that (+)3H-3-PPP labels
hippocampal pyramidal cells and granule cells in the dentate gyrus.
Intrastriatal injection of ibotenic acid dramatically reduces (+)3H-3-PPP
binding in this area, while injection of 6-hydroxydopamine produces a
relatively slight decrease. The distribution of (+)3H-3-PPP binding sites
does not correlate with the receptor distribution of any recognized
neurotransmitter or neuropeptide, including dopamine. However, there is a
notable similarity between the distribution of (+)3H-3-PPP sites and
high-affinity binding sites for psychotomimetic opioids, such as the
benzomorphan (+)SKF 10,047.
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