Selective (+)-amphetamine neurotoxicity on striatal dopamine nerve terminals in the mouse.
1 Infusion of large doses of (+)-amphetamine continuously for 7 days by means of osmotic minipumps caused a long-lasting reduction of endogenous dopamine levels, dopamine nerve terminals demonstrated histochemically and [3H]-noradrenaline uptake in vitro in the striatum of mice. 2 The effect was dose-dependent, fully developed after 4 days and selective for striatal dopamine up to a dose of (+)-amphetamine of 25 microgram/h. Higher doses, which produced increased mortality, also affected dopamine levels in the olfactory tubercle as well as noradrenaline in several regions. 3 Fluorescence histochemical studies using the Falck-Hillarp technique disclosed catecholamine accumulations in the striatum after (+)-amphetamine; a sign of neurotoxic damage. No effects on the dopamine cell bodies were noted. There were also no indications of neurotoxic damage to noradrenaline or 5-hydroxytryptamine neurones induced by (+)-amphetamine. 4 Large doses of (-)-amphetamine were without effect, demonstrating that the long-lasting impairment of transmitter uptake-storage mechanism in striatal dopamine nerve terminals is selective for (+)-amphetamine. 5 There was a slow gradual recovery of endogenous dopamine and [3H]-noradrenaline uptake in the striatum with time, which was almost complete 6 months after the (+)-amphetamine administration. 6 The results give further evidence for the view that (+)-amphetamine in large doses can have a selective neurotoxic action on a vulnerable population of a dopamine nerve terminals in the striatum. The results suggest in addition that there is a slow regrowth and regeneration with time of damaged dopamine nerve terminals.
D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D006651:Histocytochemistry; D008297:Male; D051379:Mice; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors
D001679:Biogenic Amines; D012701:Serotonin; D003913:Dextroamphetamine; D004298:Dopamine; D009638:Norepinephrine