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

Abstract

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 μM CRF into DRN increased serotonin release in both regions, whereas 0.1 μM CRF decreased and had no effect on serotonin release in DRN and mPFC, respectively. Pre-perfusion with CRF1 antagonist into DRN inhibited 0.1 μM CRF-induced serotonin reduction, whereas pre-perfusion with CRF2 antagonist in DRN inhibited 10 μM CRF-induced serotonin elevation, without affecting 0.1 μM 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.

• Authors: Shunske Tanahashi, Satoshi Yamamura, Masanori Nakagawa, Eishi Motomura, Motohiro Okada
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 220 Issue 3 Pg. 599-610 (Apr 2012) ISSN: 1432-2072 [Electronic] Germany
• PMID: 21947356 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• CRF receptor type 2
• Receptors, Corticotropin-Releasing Hormone
• Triazines
• Serotonin
• Carbamazepine
• CRF receptor type 1
• Corticotropin-Releasing Hormone
• Lamotrigine

Topics

• Animals
• Anticonvulsants (administration & dosage, pharmacology)
• Carbamazepine (administration & dosage, pharmacology)
• Corticotropin-Releasing Hormone (metabolism)
• Dose-Response Relationship, Drug
• Lamotrigine
• Male
• Microdialysis
• Mood Disorders (physiopathology)
• Prefrontal Cortex (drug effects, metabolism)
• Raphe Nuclei (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Corticotropin-Releasing Hormone (antagonists & inhibitors, metabolism)
• Serotonin (metabolism)
• Triazines (administration & dosage, pharmacology)