Repeated ketamine administration produces up-regulation of muscarinic acetylcholine receptors in the forebrain, and reduces behavioral sensitivity to scopolamine in mice.
T Morita, Shinichiro Hitomi, S Saito, T Fujita, Yoshitaka Uchihashi, H Kuribara
Psychopharmacology February 1995 DOI: 10.1007/bf02246210 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | ddY male mice |
| Interventions | Ketamine Scopolamine |
| Dose | 25 mg/kg ketamine subcutaneously every 3 days for five administrations; ketamine 12.5, 25, and 50 mg/kg in the behavioral experiment; scopolamine 0.5 mg/kg subcutaneously |
| Duration | Five administrations over 15 days |
| Measures | [3H]quinuclidinyl benzilate ([3H]QNB) receptor binding assay, locomotor activity (hyperlocomotion) |
| Topics | Esketamine Ketamine |
| Key findings | Repeated ketamine administration increased forebrain muscarinic acetylcholine receptor density in a dose-dependent manner without changing receptor affinity, and reduced scopolamine-induced hyperlocomotion at 50 mg/kg. The authors suggest these changes may reflect altered central acetylcholine transmission. |
Abstract
To study the effects of repeated ketamine administration on central muscarinic acetylcholine receptors (mAchRs), ddY male mice were administered subcutaneous doses of 25 mg/kg ketamine every 3 days for a total of five times. Receptor binding assays of mAchR were carried out in the forebrain (FB), cerebellum (CB) and brainstem (BS), using [3H]quinuclidinyl benzilate ([3H]QNB) as a ligand. In addition, we examined whether repeated ketamine (12.5, 25 and 50 mg/kg) or saline (five times) could modify the hyperlocomotion induced by scopolamine (0.5 mg/kg, SC) (a muscarinic antagonist), using a behavior-pharmacological technique. Repeating the ketamine administration resulted in a significant increase in the receptor density value (Bmax) for [3H]QNB only in FB, dependent on the numbers of administrations (1270 +/- 33 fmol/mg protein for a single dose, 1620 +/- 59 for four treatments, 1738 +/- 70 for five treatments without any change in apparent affinity (defined as the reciprocal of the dissociation constant) (Kd). A competitive inhibition study of repeated (5 times) administration of ketamine failed to detect any subtype-specific changes in mAchRs. Repeated ketamine administration reduced the scopolamine-induced hyperlocomotion in a dose-related way, and the changes were significant at 50 mg/kg. Our results suggest that repeated ketamine administration produces an up-regulation of mAchRs, and this change may be associated with altered Ach transmission in 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 |
Citations in the library
Cited by 5
- A Review of the Nonmedical Use of Ketamine: Use, Users and Consequences Journal of Psychoactive Drugs December 1, 2000
- Animal Models of Serotonergic Psychedelics ACS Chemical Neuroscience September 24, 2012
- Ketamine Psychedelic Psychotherapy: Focus on its Pharmacology, Phenomenology, and Clinical Applications International Journal of Transpersonal Studies July 1, 2014
- The nonmedical use of ketamine, part two: A review of problem use and dependence. Journal of Psychoactive Drugs 2001
- Dose-dependent effects of repeated ketamine administration on muscarinic acetylcholine receptors in the mouse forebrain. Journal of Anesthesia September 1, 1995
Cites 2
- The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate British Journal of Pharmacology June 1, 1983
- A comparison between classes of drugs having phencyclidine-like behavioral properties on dopamine efflux in vitro and dopamine metabolism in vivo. Journal of Pharmacology and Experimental Therapeutics November 1, 1984