Supersensitivity of the Cholinergic Muscarinic System in the Rat”™s Brain is Induced by High Concentrations of Cu+2

• Elsa Gutiérrez Reyes Universidad Centroccidental “Lisandro Alvarado”, Decanato de Medicina, Centro de Investigaciones Biomédicas, Unidad de Investigaciones Bioquímicas “José Antonio Moreno Yánez”
• Darwin Castañeda Perozo Universidad Centroccidental “Lisandro Alvarado”, Decanato de Medicina, Centro de Investigaciones Biomédicas, Unidad de Investigaciones Bioquímicas “José Antonio Moreno Yánez”
• Jhan Papale Centofanti Universidad Centroccidental “Lisandro Alvarado”, Decanato de Medicina, Centro de Investigaciones Biomédicas, Unidad de Investigaciones Bioquímicas “José Antonio Moreno Yánez”
• Carlota Nello Pérez Universidad Centroccidental “Lisandro Alvarado”, Decanato de Medicina, Centro de Investigaciones Biomédicas, Unidad de Investigaciones Bioquímicas “José Antonio Moreno Yánez”
• Carmine Pascuzzo Lima Universidad Centroccidental “Lisandro Alvarado”, Decanato de Medicina, Centro de Investigaciones Biomédicas, Unidad de Investigaciones Bioquímicas “José Antonio Moreno Yánez”
• José Moreno Yanez Universidad Centroccidental “Lisandro Alvarado”, Decanato de Medicina, Centro de Investigaciones Biomédicas, Unidad de Investigaciones Bioquímicas “José Antonio Moreno Yánez”
• Rafael Bonfante Cabarcas Universidad Centroccidental “Lisandro Alvarado”, Decanato de Medicina, Centro de Investigaciones Biomédicas, Unidad de Investigaciones Bioquímicas “José Antonio Moreno Yánez”

Resumen

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) 1mg/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