Dietary cadmium exposure attenuates D-amphetamine-evoked [3H]dopamine release from striatal slices and methamphetamine-induced hyperactivity.
Prolonged exposure to environmentally relevant amounts of CdCl2 results in cadmium accumulation in dopamine-rich brain regions, such as striatum. Exposure to these low levels of cadmium also diminishes cocaine-induced hyperactivity and conditioned reinforcement. The goal of the present study was to assess the effect of cadmium on amphetamine pharmacology. Direct application of cadmium (0.1-100 microM), within the concentrations reported in brain after chronic exposure, to preloaded rat striatal slices did not alter D-amphetamine-evoked [3H]dopamine release. To determine the effect of dietary cadmium exposure on amphetamines, rats received ad libitum access to diet containing CdCl2 (10 or 100 ppm) or to control diet for 30 days and then D-amphetamine-evoked [3H]dopamine release and methamphetamine-induced hyperactivity were measured. Dietary CdCl2 exposure produced a marked increase in cadmium blood and brain levels, approximate to environmental metal exposure. Dietary cadmium exposure was associated with decreased potency of D-amphetamine to evoke [3H]dopamine release. Cadmium-exposed rats were also less sensitive to the locomotor-activating effect of acute methamphetamine (0.3 or 1.0 mg/kg) injection. The present findings demonstrate that the presence of cadmium in brain is not sufficient for the inhibition of D-amphetamine-evoked dopamine release. This suggests that cadmium does not directly interfere with the mechanism of action for amphetamine pharmacology; rather, it suggests that long-term cadmium exposure induces a change in the number and/or function of striatal neurons.
Miller
Dennis K
DK
Department of Psychological Sciences, 208 McAlester Hall, University of Missouri, Columbia MO 65211, USA. millerden@missouri.edu
Dopheide
Marsha M
MM
Smith
Shawn M
SM
Casteel
Stan W
SW
D000818:Animals; D001921:Brain / Q000378:metabolism; D002104:Cadmium / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004032:Diet; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006948:Hyperkinesis / Q000139:chemically induced* / Q000523:psychology; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D002104:Cadmium; D008694:Methamphetamine; D011189:Potassium Chloride; D003913:Dextroamphetamine; D004298:Dopamine