Dose-dependent effects of repeated ketamine administration on muscarinic acetylcholine receptors in the mouse forebrain.
Shinichiro Hitomi, Toshihito Morita, Shigeru Saito, Yoshitaka Uchihashi
Journal of Anesthesia September 1, 1995 DOI: 10.1007/bf02479877 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Mice forebrain tissue |
| Interventions | Ketamine Scopolamine |
| Dose | Ketamine: 0 (saline), 12.5, 25, and 50 mg/kg every 3 days for a total of five times, subcutaneously; Scopolamine: 0.5 mg/kg |
| Duration | Five ketamine administrations every 3 days (15 days total) |
| Measures | [3H]quinuclidinyl benzilate ([3H]QNB) receptor binding assay, scopolamine-induced hyperlocomotion |
| Topics | Ketamine Esketamine |
| Keywords | Forebrain Up-regulation Muscarinic acetylcholine receptors |
| Key findings | Repeated ketamine administration increased muscarinic acetylcholine receptor density (Bmax) in mouse forebrain from 1520 fmol/mg protein in controls to 1966 and 2064 fmol/mg protein at 25 and 50 mg/kg, respectively, without changing affinity. The 50 mg/kg dose also reduced scopolamine-induced hyperlocomotion. The authors conclude that repeated ketamine up-regulates these receptors, probably reflecting altered central acetylcholine transmission. |
Abstract
To study the effects of repeated ketamine administration (0: saline, 12.5, 25, and 50 mg·kg-1 every 3 days for a total of five times, subcutaneously) on the central muscarinic acetylcholine receptors (mAchRs), receptor binding assays of mAchR were carried out in the forebrain of mice, using [3H]quinuclidinyl benzilate ([3H]QNB) as a ligand. We also examined whether repeated ketamine administration could modify the sensitivity to scopolamine (0.5 mg·kg-1) (a muscarinic antagonist). Repeated ketamine administration produced a significant increase in the receptor density values (Bmax) for [3H]QNB (1520±51 fmol·mg protein-1 for the control group, 1650±43 for the 12.5 mg·kg-1 group, 1966±70 for the 25 mg·kg-1 group and 2064±125 for the 50 mg·kg-1 group) (P<0.05, when the 25 mg·kg-1 and 50 mg·kg-1 groups were compared to the control group) without any change in apparent affinity. Repeated ketamine reduced scopolamine-induced hyperlocomotion at 50 mg·kg-1 (P<0.05). We conclude that repeated ketamine administration produces up-regulation of mAchRs, which is probably associated with the altered Ach transmission of the central nervous system.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |