Repeated ketamine administration produces up-regulation of muscarinic acetylcholine receptors in the forebrain, and reduces behavioral sensitivity to scopolamine in mice.
T Morita, S Hitomi, S Saito, T Fujita, Y 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.