[Repeated MK-801 administration but not methamphetamine produces up-regulation of muscarinic acetylcholine receptors in mice].

The author examined the effects of chronic treatment with MK-801 or methamphetamine (MAP) on the muscarinic acetylcholine receptors. Chronic treatment with MK-801 (0, 0.1, 0.5 and 1 mg.kg-1, daily treatment for 7 days) but not MAP produced an increase in total [3H] Quinuclidinyl bensilate (QNB) binding sites (Bmax) in the forebrain in a dose-dependent way without any effect of apparent affinity (the reciprocal of the dissociation constant, Kd). This was associated with the reduction in the behavior sensitivity to scopolamine (1 mg.kg-1, sc) (P < 0.05, at 0.5 and 1 mg.kg-1 compared with the control group). Coadministration of haloperidol (0, 0.125, 0.5 and 2 mg.kg-1), a dopamine receptor antagonist, prevented the up-regulation of muscarinic acetylcholine receptors (mAchR) induced by MK-801 (1 mg.kg-1) in a dose-dependent way, indicating involvement of the dopaminergic mechanism in the induction of up-regulation of mAchRs. The author concludes that chronic treatment with NMDA antagonists but not with MAP produces an up-regulation of mAchRs in the forebrain by facilitating dopamine release and these changes are associated with an alteration in Ach transmission in the central nervous system.