[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.
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Department of Anesthesiology and Reanimatology, Gunma University School of Medicine, Maebashi.
D000818:Animals; D001921:Brain / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D011976:Receptors, Muscarinic; D008694:Methamphetamine; D016291:Dizocilpine Maleate