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dc.contributor.authorLiu, Xiang
dc.contributor.authorBanister, Samuel D
dc.contributor.authorChristie, MacDonald J
dc.contributor.authorBanati, Richard
dc.contributor.authorMeikle, Steve
dc.contributor.authorCoster, Mark J
dc.contributor.authorKassiou, Michael
dc.date.accessioned2017-05-03T15:16:47Z
dc.date.available2017-05-03T15:16:47Z
dc.date.issued2007
dc.date.modified2009-04-20T04:47:18Z
dc.identifier.issn0014-2999
dc.identifier.doi10.1016/j.ejphar.2006.10.020
dc.identifier.urihttp://hdl.handle.net/10072/22620
dc.description.abstractTrishomocubane analogs TC1 (I) and TC4 (II) were evaluated for their modulatory effects on locomotor activity as well as interactions with cocaine-induced responses. TC1 and TC4 have high affinity and moderate to high selectivity for s1 (Ki = 10 nM, s1/s2 = 0.03) and s2 (Ki = 20 nM, s1/s2 = 7.6) receptor subtypes resp. Both compds. have negligible affinity for the dopamine (DAT), serotonin (SERT), and norepinephrine (NET) transporters. In behavioral studies, TC1 produced a dose-related inhibition in spontaneous locomotor activity measured in a Digiscan app. TC1 attenuated the stimulatory locomotor effect of 20 mg/kg cocaine with a half-maximal depressant activity (ID50) of 38.6 mg/kg. TC1 (dose range of 25 to 100 mg/kg) also partially substituted for the effect of cocaine (10 mg/kg) in a discriminative stimulus task, involving the trained discrimination between cocaine and saline using a two-lever choice method. Following a dose of 50 mg/kg TC1, a max. of 31% substitution was reached. The response rate was reduced to 56% of vehicle control following a TC1 dose of 100 mg/kg. These behavioral effects suggest that TC1 can act as an antagonist via the s1 receptor. In contrast to TC1, TC4 produced a stimulant effect in locomotor activity with the ED50 estd. at 0.94 mg/kg. In addn., TC4 failed to inhibit cocaine-induced stimulation; neither did it substitute for the discriminative stimulus effects of cocaine. TC4 thus appears to interact predominantly with the s2 receptor subtype (s1/s2 = 7.6) which may result in dopamine stimulation independent of the effects of cocaine. The differential effect of TC1 and TC4 warrants further study of the mechanism of these actions. Present data also suggests a potential role for trishomocubane analogs in developing medication or research tools for cocaine addiction.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.publisher.placeNew York
dc.publisher.urihttp://www.sciencedirect.com/science/journal/00142999
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom37
dc.relation.ispartofpageto42
dc.relation.ispartofissue1
dc.relation.ispartofjournalEuropean Journal of Pharmacology
dc.relation.ispartofvolume555
dc.rights.retentionN
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchCognitive and computational psychology
dc.subject.fieldofresearchcode3214
dc.subject.fieldofresearchcode5204
dc.titleTrishomocubanes: Novel σ ligands modulate cocaine-induced behavioural effects
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2007
gro.hasfulltextNo Full Text
gro.griffith.authorCoster, Mark J.


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