Raphe AMPA receptors and nicotinic acetylcholine receptors mediate ketamine-induced serotonin release in the rat prefrontal cortex. (August 2014)

• Record Type: Journal Article
• Authors: Nishitani, Naoya; Nagayasu, Kazuki; Asaoka, Nozomi; Yamashiro, Mayumi; Shirakawa, Hisashi; Nakagawa, Takayuki; Kaneko, Shuji
• Is Part Of: International journal of neuropsychopharmacology. Volume 17:Number 8(2014)
• Page Start: 1321
• Page End: 1326
• Publication Date: 2014-08
• Subjects: Neuropsychopharmacology -- Periodicals; Neuropharmacology -- Periodicals; Psychopharmacology -- Periodicals; 615.78
• DOI: 10.1017/S1461145714000649
• Languages: English
• ISSNs: 1461-1457

Abstract

<abstract abstract-type="normal"> <title>Abstract</title> <p>Several lines of evidence indicate that ketamine has a rapid antidepressant-like effect in rodents and humans, but underlying mechanisms are unclear. In the present study, we investigated the effect of ketamine on serotonin (5-HT) release in the rat prefrontal cortex by <italic>in vivo</italic> microdialysis. A subcutaneous administration of ketamine (5 and 25 mg/kg) significantly increased the prefrontal 5-HT level in a dose-dependent manner, which was attenuated by local injection of <italic>α</italic>-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antagonists into the dorsal raphe nucleus (DRN). Direct stimulation of AMPARs in the DRN significantly increased prefrontal 5-HT level, while intra-DRN injection of ketamine (36.5 nmol) had no effect. Furthermore, intra-DRN injection of an <italic>α</italic>₄<italic>β</italic>₂-nicotinic acetylcholine receptor (nAChR) antagonist, dihydro-<italic>β</italic>-erythroidine (10 nmol), significantly attenuated the subcutaneous ketamine-induced increase in prefrontal 5-HT levels. These results suggest that AMPARs and <italic>α</italic>₄<italic>β</italic>₂-nAChRs in the DRN play a key role in the ketamine-induced 5-HT release in the prefrontal cortex.</p> </abstract>