Reversible and irreversible phases of serotonin depletion by 4-chloroamphetamine.
Pretreatment of rats with an agent that inhibits uptake into serotoninergic neurons [Lilly 110140: 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine hydrochloride] prevented the depletion of brain serotonin by 4-chloroamphetamine, presumably by preventing the entry of 4-chloroamphetamine into the serotonin neuron. When the uptake inhibitor was given after 4-chloroamphetamine, the lowering of both serotonin and tryptophan hydroxylase levels in brain was reversed. Serotonin levels returned to normal after 110140 administration to 4-chloroamphetamine-treated rats at a rate similar to the calculated rate of serotonin turnover in rats treated with 110140 alone. Progressively less reversibility of the 4-chloroamphetamine effect occurred when 110140 was injected at 8, 16 and 24 hr after 4-chloroamphetamine, and no reversibility was observed when 110140 was injected at 32 or 48 hr after 4-chloroamphetamine. These findings indicate that the depletion of brain serotonin by 4-chloroamphetamine is initially reversible but that there is a gradual transition into an irreversible effect between 24 and 48 hr after 4-chloroamphetamine injection. Apparently the prolonged presence of 4-chloroamphetamine inside the serotonin neuron produced by continual reuptake of 4-chloroamphetamine is required for the semi-permanent depletion of brain serotonin stores.
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D010134:Fenclonine / Q000494:pharmacology; D008297:Male; D010647:Phenyl Ethers / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D010133:p-Chloroamphetamine / Q000494:pharmacology*
D000662:Amphetamines; D010647:Phenyl Ethers; D011437:Propylamines; D012701:Serotonin; D010133:p-Chloroamphetamine; D014365:Tryptophan Hydroxylase; D010134:Fenclonine