title: Supersensitivity of the cholinergic muscarinic system in the rat's brain is induced by high concentrations of Cu+2.
abstract: Transition metals have been described as regulators of receptor's function. here, we studied the effects of chronic administration of Cu2+ or the Cu2+ chelator penicillamine (PA) on the functional and binding properties of the muscarinic receptors (MR) on selected areas of rat's brain. Groups of 10 Sprague-Dawley rats were treated daily, for 45 days with either 1) 1 mg/Kg CuSO4 (Cu2+), 2) 100 mg/Kg PA, or 3) saline solution. Double T-maze and motility cages were used for behavioral testing and the binding assays were performed using [3H]-QNB or [3H]-N-MSCP as MR's ligands. Cu2+ brain levels were measured in the cerebral cortex by atomic absorption spectrophotometer. Results showed that PA treated rats displayed a significant decrease of locomotor's activity (LA) and rearing behavior (RB), but a significant increases in memory efficiency (ME). Cu2+ treated rats displayed diminished RB with no significant changes in LA. Cu2+ treated rats displayed higher MR's density (Bmax) in cortex (C), striatum (S), and hippocampus (H). An increase in Bmax was also observed in PA treated rats, but only in C and S. Finally, Cu2+ tissue concentration was significantly higher in C of both Cu2+ and with PA treated animals. In conclusion, 45 days of Cu2+ or PA treatment induced brain hypercuprosis, which was associated with MR binding supersensitivity; however, change in ME was only observed in PA treated rats suggesting that might be still another factor in these experiments besides Cu2+ (i.e., Zn2+ or PA itself) involved in memory modulation.
authors.affiliation: Unidad de Investigaciones Bioquímicas José Antonio Moreno Yánez, Centro de Investigaciones Biomédicas, Decanato de Medicina, Universidad Centroccidental Lisandro Alvarado, Barquisimeto, Venezuela.
authors.forename: Elsa
authors.initials: E
authors.lastname: Gutiérrez-Reyes
authors.forename: Darwin
authors.initials: D
authors.lastname: Castañeda-Perozo
authors.forename: Jhan
authors.initials: J
authors.lastname: Papale-Centofanti
authors.forename: Carlota
authors.initials: C
authors.lastname: Nello-Pérez
authors.forename: Carmine
authors.initials: C
authors.lastname: Pascuzzo-Lima
authors.forename: José
authors.initials: J
authors.lastname: Moreno-Yanez
authors.forename: Rafael
authors.initials: R
authors.lastname: Bonfante-Cabarcas
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology; D019327:Copper Sulfate / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000187:drug effects*; D010396:Penicillamine / Q000494:pharmacology; D011736:Pyridoxine / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D019287:Zinc Sulfate / Q000494:pharmacology
chemical_list: D002614:Chelating Agents; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D009419:Nerve Tissue Proteins; D011976:Receptors, Muscarinic; C028484:quinuclidinyl benzilate receptor; D011813:Quinuclidinyl Benzilate; D019287:Zinc Sulfate; D001285:Atropine; D010396:Penicillamine; D011736:Pyridoxine; D019327:Copper Sulfate