Dose-dependent effects of repeated ketamine administration on muscarinic acetylcholine receptors in the mouse forebrain.

To study the effects of repeated ketamine administration (0: saline, 12.5, 25, and 50 mg·kg 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 [H]quinuclidinyl benzilate ([H]QNB) as a ligand. We also examined whether repeated ketamine administration could modify the sensitivity to scopolamine (0.5 mg·kg) (a muscarinic antagonist). Repeated ketamine administration produced a significant increase in the receptor density values (Bmax) for [H]QNB (1520±51 fmol·mg protein for the control group, 1650±43 for the 12.5 mg·kg group, 1966±70 for the 25 mg·kg group and 2064±125 for the 50 mg·kg group) (P<0.05, when the 25 mg·kg and 50 mg·kg groups were compared to the control group) without any change in apparent affinity. Repeated ketamine reduced scopolamine-induced hyperlocomotion at 50 mg·kg (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.