UNIVERSI
TÄ
TS-
BIBLIOTHEK
P
ADERBORN
Anmelden
Menü
Menü
Start
Hilfe
Blog
Weitere Dienste
Neuerwerbungslisten
Fachsystematik Bücher
Erwerbungsvorschlag
Bestellung aus dem Magazin
Fernleihe
Einstellungen
Sprache
Deutsch
Deutsch
Englisch
Farbschema
Hell
Dunkel
Automatisch
Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist
gegebenenfalls
nur via VPN oder Shibboleth (DFN-AAI) möglich.
mehr Informationen...
Universitätsbibliothek
Katalog
Suche
Details
Zur Ergebnisliste
Ergebnis 17 von 478
Datensatz exportieren als...
BibTeX
Cocaine occupancy of sigma1 receptors and dopamine transporters in mice
Synapse (New York, N.Y.), 2016-03, Vol.70 (3), p.98-111
Lever, John R.
Fergason-Cantrell, Emily A.
Watkinson, Lisa D.
Carmack, Terry L.
Lord, Sarah A.
Xu, Rong
Miller, Dennis K.
Lever, Susan Z.
2016
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Lever, John R.
Fergason-Cantrell, Emily A.
Watkinson, Lisa D.
Carmack, Terry L.
Lord, Sarah A.
Xu, Rong
Miller, Dennis K.
Lever, Susan Z.
Titel
Cocaine occupancy of sigma1 receptors and dopamine transporters in mice
Ist Teil von
Synapse (New York, N.Y.), 2016-03, Vol.70 (3), p.98-111
Ort / Verlag
United States: Blackwell Publishing Ltd
Erscheinungsjahr
2016
Quelle
MEDLINE
Beschreibungen/Notizen
ABSTRACT Activation of sigma1 (σ1) receptors contributes to the behavioral and toxic effects of (−)‐cocaine. We studied a key step, the ability of (−)‐cocaine to occupy σ1 receptors in vivo, using CD‐1® mice and the novel radioligand [125I]E‐N−1‐(3′‐iodoallyl)‐N′‐4‐(3″,4″‐dimethoxyphenethyl)‐piperazine ([125I]E‐IA‐DM‐PE‐PIPZE). (−)‐Cocaine displayed an ED50 of 68 μmol/kg for inhibition of specific radioligand binding in whole brain, with values between 73 and 80 μmol/kg for heart, lung, and spleen. For comparison, an ED50 of 26 μmol/kg for (−)‐cocaine occupancy of striatal dopamine transporters (DAT) was determined by inhibition of [125I]3β‐(4‐iodophenyl)tropan‐2β‐carboxylic acid isopropyl ester ([125I]RTI‐121) binding. A chief finding is the relatively small potency difference between (−)‐cocaine occupancy of σ1 receptors and the DAT, although the DAT occupancy is likely underestimated. Interactions of (−)‐cocaine with σ1 receptors were assessed further using [125I]E‐IA‐DM‐PE‐PIPZE for regional cerebral biodistribution studies and quantitative ex vivo autoradiography of brain sections. (−)‐Cocaine binding to cerebral σ1 receptors proved directly proportional to the relative site densities known for the brain regions. Nonradioactive E‐IA‐DM‐PE‐PIPZE gave an ED50 of 0.23 μmol/kg for occupancy of cerebral σ1 receptors, and a 3.16 μmol/kg (i.p.) dose attenuated (−)‐cocaine‐induced locomotor hyperactivity by 30%. This effect did not reach statistical significance, but suggests that E‐IA‐DM‐PE‐PIPZE is a probable σ1 receptor antagonist. As groundwork for the in vivo studies, we used standard techniques in vitro to determine ligand affinities, site densities, and pharmacological profiles for the σ1 and σ2 receptors expressed in CD‐1® mouse brain. Synapse 70:98–111, 2016. © 2016 Wiley Periodicals, Inc. Cocaine exhibits substantial occupancy of cerebral σ1 receptors in mice, ED50 68 µmol / kg (∼ 20 mg / kg). Ex vivo autoradiography shows uniform interactions of the drug with σ1 receptors throughout the brain, with inhibition of radioligand binding proportional to the site densities of the various brain regions.
Sprache
Englisch
Identifikatoren
ISSN: 0887-4476
eISSN: 1098-2396
DOI: 10.1002/syn.21877
Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4724290
Format
–
Schlagworte
Animals
,
Autoradiography
,
Binding, Competitive
,
Brain - drug effects
,
Brain - metabolism
,
Cocaine
,
Cocaine - pharmacokinetics
,
Cocaine - pharmacology
,
Dopamine
,
Dopamine Plasma Membrane Transport Proteins - metabolism
,
dopamine transporter
,
Dopamine Uptake Inhibitors - pharmacokinetics
,
Dopamine Uptake Inhibitors - pharmacology
,
Dose-Response Relationship, Drug
,
locomotor activity
,
Male
,
Mice
,
Motor Activity - drug effects
,
mouse
,
occupancy
,
Receptors, sigma - metabolism
,
sigma receptor
,
Sigma-1 Receptor
,
substance abuse
Weiterführende Literatur
Empfehlungen zum selben Thema automatisch vorgeschlagen von
bX