Pharmacological doses of Zn2+ induce a muscarinic cholinergic supersensitivity

The goal of this study was to evaluate the effect of chronic Zn2+ administration (1 mg/kg/day for 1 month) in Sprague-Dawley rats (n = 11) on motility and rearing behaviors (number of events/10 min measured in motility cage), on memory (percentage of failures using a foot-shock double T maze), on the number of muscarinic receptors (using [(3)H]-QNB as a marker) and on the cholinacetyltransferase (Chat) activity (determined by Fonnun's method) in various brain areas (striatum, hippocampus and frontal cortex), as compared with saline-treated rats (n = 10). Our results showed that Zn2+ induced a decrease in rearing (control: 24.6 +/- 3; Zn2+: 15.91 +/- 2.19) and in locomotor activity (control: 37 +/- 3.79; Zn2+: 25 +/- 4.37), a decrease in failures during memory trials (control: 26.12 +/- 5.6; Zn2+: 5.33 +/- 2.71) and an increase in muscarinic receptor density (fmol/mg) in the striatum (control: 539 +/- 6.18; Zn2+: 720 +/- 14.69), hippocampus (control: 396 +/- 7.41; Zn 2+: 458 +/- 5.05) and frontal cortex (control: 506 +/- 10.28; Zn2+: 716 +/- 16.54). Chat activity (pmol/mg/min) was decreased only in the striatum (control: 4240 +/- 158; Zn2+: 2311 +/- 69). We conclude that Zn 2+ induces a cholinergic functional supersensitivity which is related to receptor upregulation.