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.
Subject(s)
Animals , Male , Rats , Copper Sulfate , Nerve Tissue Proteins/drug effects , Brain Chemistry/drug effects , Receptors, Muscarinic/drug effects , Muscarinic Agonists/pharmacology , Muscarinic Antagonists/pharmacology , Atropine , Chelating Agents , Copper Sulfate , Corpus Striatum , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Dose-Response Relationship, Drug , Cholinergic Fibers/drug effects , Cholinergic Fibers/physiology , Hippocampus , Maze Learning , Memory , Motor Activity , Penicillamine , Pyridoxine , Quinuclidinyl Benzilate , Radioligand Assay , Rats, Sprague-Dawley , Receptors, Muscarinic/metabolism , Zinc SulfateABSTRACT
Vascular autonomic receptors in amphibians exhibit difference from more evolved mammalian species. Vascular perfusion studies in frog indicate constrictions by prominent muscarinic but rudimentary nicotinic constrictive regulation by cholinergic systems. Difference from classical effect-patterns of pharmacological interventions, observed in the study, make room to visualise complexity of additional regulatory mechanisms.