Open AccessAsenapine modulates mood‐related behaviors and 5‐ HT 1A/7 receptors‐mediated neurotransmission
Author(s) -
Delcourte Sarah,
Abrial Erika,
Etiévant Adeline,
Rovera Renaud,
Arnt Jørn,
Didriksen Michael,
Haddjeri Nasser
Publication year - 2017
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12698
Subject(s) - asenapine , serotonergic , pharmacology , 5 ht receptor , behavioural despair test , agonist , dopaminergic , chemistry , dorsal raphe nucleus , receptor , antidepressant , serotonin , medicine , bipolar disorder , lithium (medication) , dopamine , hippocampus
Summary Aim Asenapine is a new atypical antipsychotic prescribed for the treatment of psychosis/bipolar disorders that presents higher affinity for serotonergic than dopaminergic receptors. The objective of this study was to investigate its antidepressant‐like and antimanic‐like properties on relevant animal models of depression and mania and to assess the acute and chronic effect of Asenapine on dorsal raphe nucleus ( DRN ) 5‐ HT cell firing activity. Methods We assessed the effects of Asenapine using in vivo electrophysiological and behavioral assays in rats. Results Behavioral experiments showed that Asenapine had no significant effect on immobility time in the forced swim test ( FST ) in control rats. In the ACTH ‐treated rats, a model of antidepressant‐resistance, Asenapine failed to alter immobility time in the FST . In contrast in the sleep deprivation ( SD ) model of mania, acute administration of Asenapine significantly decreased the hyperlocomotion of SD rats. In the DRN , acute administration of Asenapine reduced the suppressant effect of the selective 5‐ HT 7 receptor agonist LP ‐44 and of the prototypical 5‐ HT 1A receptor agonist 8‐ OH ‐ DPAT on 5‐ HT neuronal firing activity. In addition, chronic treatment with Asenapine enhanced DRN 5‐ HT neuronal firing and this effect was associated with an alteration of the 5‐ HT 7 receptor responsiveness. Conclusion These results confirm that Asenapine displays robust antimanic property and effective in vivo antagonistic activity at 5‐ HT 1A/7 receptors.