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.

Increase of striatal dopamine release by cadmium in nursing rats and its prevention by dexamethasone-induced metallothionein.

Repeated daily intraperitoneal (i.p.) administrations of cadmium (CdCl2, 1 mg/kg per day for 5 days) increased striatal dopamine (DA) release (180% of controls) and turnover (150% of controls) in 13-day-old rats. Cd treatment also increased striatal metallothionein (MT) content (161%), Cd (127%) and lipid peroxidation (LPO, 190%). In addition, Cd treatment decreased striatal tyrosine hydroxylase (TH) activity (-28%), and such an effect may result from D-2 receptor blockade as a consequence of excessive dopamine release, since sulpiride (a specific D-2 receptor antagonist) administration to Cd-treated rats abolished the effect of Cd on TH. No effect was observed on striatal monoamine oxidase (MAO) activity. Dexamethasone (Dx) treatment increased striatal MT content and caused no effect on either DA release or turnover. However, Dx administration prevented the effects caused by Cd, including the increased DA release and enhanced striatal lipid peroxidation. These results indicate that toxic effects on the brain are to be expected as a result of Cd exposure and that Dx administration can attenuate them.