RGD Reference Report - Effect of lamotrigine and carbamazepine on corticotropin-releasing factor-associated serotonergic transmission in rat dorsal raphe nucleus. - Rat Genome Database

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Effect of lamotrigine and carbamazepine on corticotropin-releasing factor-associated serotonergic transmission in rat dorsal raphe nucleus.

Authors: Tanahashi, S  Yamamura, S  Nakagawa, M  Motomura, E  Okada, M 
Citation: Tanahashi S, etal., Psychopharmacology (Berl). 2011 Sep 27.
RGD ID: 5507821
Pubmed: PMID:21947356   (View Abstract at PubMed)
DOI: DOI:10.1007/s00213-011-2506-y   (Journal Full-text)

Corticotropin-releasing factor (CRF) and serotonin are important transmitters of the pathophysiology of mood disorder. To clarify the mechanisms of action of lamotrigine (LTG) and carbamazepine (CBZ), we determined their effects on serotonin release associated with CRF in rat dorsal raphe nucleus (DRN) and median prefrontal cortex (mPFC) using dual-probe microdialysis. Neither perfusion with CRF1 nor CRF2 antagonists into DRN-affected serotonin release in DRN and mPFC. Perfusion of 10 muM CRF into DRN increased serotonin release in both regions, whereas 0.1 muM CRF decreased and had no effect on serotonin release in DRN and mPFC, respectively. Pre-perfusion with CRF1 antagonist into DRN inhibited 0.1 muM CRF-induced serotonin reduction, whereas pre-perfusion with CRF2 antagonist in DRN inhibited 10 muM CRF-induced serotonin elevation, without affecting 0.1 muM CRF-induced serotonin reduction. LTG perfusion concentration dependently decreased serotonin releases in DRN and mPFC. Therapeutic and supratherapeutic concentrations of CBZ increased and decreased serotonin releases in both regions, respectively. Pre-perfusion with sub-therapeutic concentration LTG inhibited CRF1-induced serotonin reduction without affecting CRF2-induced serotonin release, whereas pre-perfusion with therapeutic concentration of LTG inhibited both CRF1- and CRF2-actions. In contrast, both therapeutic and supratherapeutic concentrations of CBZ inhibited CRF2-induced serotonin release without affecting CRF1-induced serotonin reduction. Neither LTG nor CBZ affected the CRF-induced cAMP production in cells over-expressing CRF1 and CRF2 receptors. This study demonstrated that inhibition of CRF2-receptor-mediated serotonergic transmission is a mechanism shared by LTG and CBZ, two clinically related compounds, whereas LTG but not CBZ inhibits CRF1-receptor-mediated serotonergic transmission. Therefore, these mechanisms may contribute to the clinical actions of these agents.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
regulation of serotonin secretion  IDA 5507821 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Crh  (corticotropin releasing hormone)


Additional Information