Content area
Full text
http://crossmark.crossref.org/dialog/?doi=10.1007/s00406-016-0692-7&domain=pdf
Web End = Eur Arch Psychiatry Clin Neurosci (2017) 267:173176 DOI 10.1007/s00406-016-0692-7
SHORT COMMUNICATION
http://crossmark.crossref.org/dialog/?doi=10.1007/s00406-016-0692-7&domain=pdf
Web End = Reduction of dopamine D2/3 receptor binding in the striatum after a single administration of esketamine, but not Rketamine: a PET study in conscious monkeys
Kenji Hashimoto1 Takeharu Kakiuchi2 Hiroyuki Ohba2 Shingo Nishiyama2 Hideo Tsukada2
Abstract R-ketamine appears to be a potent, long-lasting and safer antidepressant, relative to esketamine (S-ketamine), since it might be free of psychotomimetic side effects. Using [11C]raclopride and positron emission tomography (PET), we investigated whether esketamine and R-ketamine can affect dopamine D2/3 receptor binding in the conscious monkey brain. A single infusion of esketa-mine (0.5 mg/kg), but not R-ketamine (0.5 mg/kg), caused a reduction of binding availability of dopamine D2/3 receptor in the monkey striatum. This study suggests that unlike to R-ketamine, esketamine can cause dopamine release in the striatum, and that its release might be associated with psychotomimetic effects of esketamine.
Keywords Dopamine D2/3 receptor Esketamine Release R-ketamine Monkey
Introduction
The rapid-onset antidepressant effects of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine have attracted serious attention after it was found that a single sub-anesthetic dose (0.5 mg/kg) of ketamine elicited a rapid antidepressant effect within 12 h, in depressed patients, including those with treatment-resistant depression and
Received: 19 February 2016 / Accepted: 11 April 2016 / Published online: 18 April 2016 The Author(s) 2016. This article is published with open access at Springerlink.com
treatment-resistant bipolar depression [14]. These benecial effects persist for up to 2 weeks in some patients. A recent meta-analysis demonstrated that ketamine produced a rapid, yet transient, antidepressant effect, with odds ratios for response and transient remission of symptoms at 24 h equaling 9.87 and 14.7, respectively, accompanied by brief psychotomimetic and dissociative effects [5].
Ketamine (or RS-ketamine) is a racemic mixture containing equal parts of R-ketamine and S-ketamine (esketa-mine). Esketamine shows an approximately threefold to fourfold greater anesthetic potency and greater undesirable psychotomimetic side effects, compared with R-ketamine [6]. This is related to the fact that esketamine has an approximately fourfold greater afnity for the NMDA receptor relative to R-ketamine [6]. We reported that R-ketamine shows greater potency and longer-lasting antidepressant effects than esketamine in animal depression models, including neonatal dexamethasone exposure, repeated social defeat stress and learned helplessness,...