l-Stepholidine-induced excitation of dopamine neurons in rat ventral tegmental area is associated with its 5-HT(1A) receptor partial agonistic activity.
Synapse
; 65(5): 379-87, 2011 May.
Article
em En
| MEDLINE
| ID: mdl-20803620
ABSTRACT
RATIONALE l-Stepholidine (l-SPD), a tetrahydroprotoberberine alkaloid, possesses a pharmacological profile of a D1/5-HT(1A) agonist and a D2 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 D2-like receptors antagonist raclopride. Collectively, these results indicate that l-SPD excited VTA DA neurons requiring its D2-like receptors antagonistic activity and 5-HT(1A) receptor agonistic activity.CONCLUSION:
The present data demonstrate that D2 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Berberina
/
Dopamina
/
Área Tegmentar Ventral
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Agonistas de Dopamina
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Receptor 5-HT1A de Serotonina
/
Neurônios
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article