Monoamine uptake in brain synaptosomes after administration of copper to rats.
In our previous studies, divalent copper (Cu) has proved to be a potent inhibitor of monoamine uptake in rat brain synaptosomes in vitro. To study whether Cu affects monoamine uptake in the brain in vivo, rats were given Cu (as CuCl2) acutely as a single dose of 30, 100, 200 or 300 mg/kg by gavage, intravenously 9 mg/kg or subacutely in drinking water, 200, 400, or 600 mg/l Cu for 3 weeks. Control animals were given deionized water. Cu was an order of magnitude more toxic intravenously than orally as judged by the Cu dose. The high affinity uptake of dopamine, 5-hydroxytryptamine and noradrenaline did not change in striatal, hypothalamic and cortical synaptosomes, respectively, after these Cu administrations. A single dose of 300 mg/kg Cu orally was lethal and increased hypothalamic Cu by 13% and cortical Cu by 26%. Lower doses increased neither blood nor brain Cu significantly 24 hrs after administration of Cu. After the 3 week administration of 600 mg/l Cu in drinking water blood Cu had increased by 22% and cerebral Cu by 19%. The results indicate that Cu is not liable to affect monoamine uptake in nerve endings in vivo. This may be explained by effective endogenous protective mechanisms against Cu.
D000042:Absorption; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D003300:Copper / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism*
D002395:Catecholamines; D012701:Serotonin; D003300:Copper; D004298:Dopamine; D009638:Norepinephrine