File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: l-Stepholidine-induced excitation of dopamine neurons in rat ventral tegmental area is associated with its 5-HT 1A receptor partial agonistic activity

Titlel-Stepholidine-induced excitation of dopamine neurons in rat ventral tegmental area is associated with its 5-HT 1A receptor partial agonistic activity
Authors
KeywordsDopamine
l-stepholidine
Schizophrenia
Serotonin
Single unit recording
Slow oscillation
Issue Date2011
PublisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/36341/home
Citation
Synapse, 2011, v. 65 n. 5, p. 379-387 How to Cite?
AbstractRationale: l-Stepholidine (l-SPD), a tetrahydroprotoberberine alkaloid, possesses a pharmacological profile of a D 1/5-HT 1A agonist and a D 2 antagonist. This unique pharmacological profile makes it a promising novel antipsychotic candidate. Preliminary clinical trials and animal experiments suggest that l-SPD improves both positive and negative symptoms of schizophrenia without producing significant extrapyramidal side effects. To further explore the antipsychotic mechanisms of the drug, we studied the effects of l-SPD on the activity of dopamine (DA) neurons in the ventral tegmental area (VTA) using in vivo single-unit recording technique in rats. Result: We found that l-SPD increased VTA DA neurons firing rate and induced slow oscillation in firing pattern. Moreover, l-SPD, not clozapine, reversed d-amphetamine-induced inhibition which induced an excitation of VTA DA neurons. Furthermore, our data indicated that the excitatory effect of l-SPD is associated with its partial agonistic action for the 5-HT 1A receptor since the 5-HT 1A receptor antagonist WAY100635 could block the l-SPD-induced excitatory effect. However, activation of 5-HT 1A receptor alone by specific agonist (±)-8-Hydroxy-2-(dipropylamino) tetralin (8-OH-DPAT) was insufficient to elicit excitation of VTA DA neurons, but the excitation of 8-OH-DPAT on VTA DA neurons was elicited in the presence of D 2-like receptors antagonist raclopride. Collectively, these results indicate that l-SPD excited VTA DA neurons requiring its D 2-like receptors antagonistic activity and 5-HT 1A receptor agonistic activity. Conclusion: The present data demonstrate that D 2 receptor antagonist/5-HT 1A receptor agonistic dual properties modulate dopaminergic transmission in a unique pattern that may underlie the different therapeutic responses between l-SPD and other atypical antipsychotic drugs. Synapse, 2010. © 2010 Wiley-Liss, Inc. Copyright © 2010 Wiley-Liss, Inc..
Persistent Identifierhttp://hdl.handle.net/10722/127584
ISSN
2015 Impact Factor: 2.026
2015 SCImago Journal Rankings: 1.059
ISI Accession Number ID
Funding AgencyGrant Number
Ministry of Science and Technology of China2007AA02z163
2009CB522201
Natural Science Foundation of China30770662
30825042
30672448
National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program''2009ZX09301-001
2009ZX09102-023
Funding Information:

Contract grant sponsor: 973 and 863-plan of the Ministry of Science and Technology of China; Contract grant numbers: 2007AA02z163, 2009CB522201; Contract grant sponsor: Natural Science Foundation of China; Contract grant numbers: 30770662, 30825042, 30672448; Contract grant sponsor: National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program''; Contract grant numbers: 2009ZX09301-001, 2009ZX09102-023

References

 

DC FieldValueLanguage
dc.contributor.authorGao, Men_HK
dc.contributor.authorChu, HYen_HK
dc.contributor.authorJin, GZen_HK
dc.contributor.authorZhang, ZJen_HK
dc.contributor.authorWu, Jen_HK
dc.contributor.authorZhen, XCen_HK
dc.date.accessioned2010-10-31T13:34:02Z-
dc.date.available2010-10-31T13:34:02Z-
dc.date.issued2011en_HK
dc.identifier.citationSynapse, 2011, v. 65 n. 5, p. 379-387en_HK
dc.identifier.issn0887-4476en_HK
dc.identifier.urihttp://hdl.handle.net/10722/127584-
dc.description.abstractRationale: l-Stepholidine (l-SPD), a tetrahydroprotoberberine alkaloid, possesses a pharmacological profile of a D 1/5-HT 1A agonist and a D 2 antagonist. This unique pharmacological profile makes it a promising novel antipsychotic candidate. Preliminary clinical trials and animal experiments suggest that l-SPD improves both positive and negative symptoms of schizophrenia without producing significant extrapyramidal side effects. To further explore the antipsychotic mechanisms of the drug, we studied the effects of l-SPD on the activity of dopamine (DA) neurons in the ventral tegmental area (VTA) using in vivo single-unit recording technique in rats. Result: We found that l-SPD increased VTA DA neurons firing rate and induced slow oscillation in firing pattern. Moreover, l-SPD, not clozapine, reversed d-amphetamine-induced inhibition which induced an excitation of VTA DA neurons. Furthermore, our data indicated that the excitatory effect of l-SPD is associated with its partial agonistic action for the 5-HT 1A receptor since the 5-HT 1A receptor antagonist WAY100635 could block the l-SPD-induced excitatory effect. However, activation of 5-HT 1A receptor alone by specific agonist (±)-8-Hydroxy-2-(dipropylamino) tetralin (8-OH-DPAT) was insufficient to elicit excitation of VTA DA neurons, but the excitation of 8-OH-DPAT on VTA DA neurons was elicited in the presence of D 2-like receptors antagonist raclopride. Collectively, these results indicate that l-SPD excited VTA DA neurons requiring its D 2-like receptors antagonistic activity and 5-HT 1A receptor agonistic activity. Conclusion: The present data demonstrate that D 2 receptor antagonist/5-HT 1A receptor agonistic dual properties modulate dopaminergic transmission in a unique pattern that may underlie the different therapeutic responses between l-SPD and other atypical antipsychotic drugs. Synapse, 2010. © 2010 Wiley-Liss, Inc. Copyright © 2010 Wiley-Liss, Inc..en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/36341/homeen_HK
dc.relation.ispartofSynapseen_HK
dc.rightsSynapse (New York). Copyright © John Wiley & Sons, Inc..-
dc.subjectDopamineen_HK
dc.subjectl-stepholidineen_HK
dc.subjectSchizophreniaen_HK
dc.subjectSerotoninen_HK
dc.subjectSingle unit recordingen_HK
dc.subjectSlow oscillationen_HK
dc.subject.meshBerberine - analogs and derivatives - pharmacology-
dc.subject.meshDopamine - metabolism-
dc.subject.meshDopamine Agonists - pharmacology-
dc.subject.meshNeurons - drug effects-
dc.subject.meshReceptor, Serotonin, 5-HT1A - metabolism-
dc.titlel-Stepholidine-induced excitation of dopamine neurons in rat ventral tegmental area is associated with its 5-HT 1A receptor partial agonistic activityen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0887-4476&volume=65&issue=5&spage=379&epage=387&date=2011&atitle=l-Stepholidine-induced+excitation+of+dopamine+neurons+in+rat+ventral+tegmental+area+is+associated+with+its+5-HT1A+receptor+partial+agonistic+activity-
dc.identifier.emailZhang, ZJ: zhangzj@hkucc.hku.hken_HK
dc.identifier.authorityZhang, ZJ=rp01297en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/syn.20855en_HK
dc.identifier.pmid20803620-
dc.identifier.scopuseid_2-s2.0-79952203392en_HK
dc.identifier.hkuros174205en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79952203392&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume65en_HK
dc.identifier.issue5en_HK
dc.identifier.spage379en_HK
dc.identifier.epage387en_HK
dc.identifier.isiWOS:000288079700003-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridGao, M=15834774500en_HK
dc.identifier.scopusauthoridChu, HY=36518470800en_HK
dc.identifier.scopusauthoridJin, GZ=7401563031en_HK
dc.identifier.scopusauthoridZhang, ZJ=8061473900en_HK
dc.identifier.scopusauthoridWu, J=36462767400en_HK
dc.identifier.scopusauthoridZhen, XC=16246797700en_HK
dc.identifier.citeulike9166268-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats