• DOI:10.1111/j.2042-7158.1974.tb09206.x
• Corpus ID: 41833796

Long‐lasting reduction of brain 5‐hydroxytryptamine concentration by 3‐chloroamphetamine and 4‐chloroamphetamine in iprindole‐treated rats

@article{Fuller1974LonglastingRO,
  title={Long‐lasting reduction of brain 5‐hydroxytryptamine concentration by 3‐chloroamphetamine and 4‐chloroamphetamine in iprindole‐treated rats},
  author={Ray W. Fuller and John C. Baker},
  journal={Journal of Pharmacy and Pharmacology},
  year={1974},
  volume={26}
}

• R. Fuller, J. Baker
• Published 1 November 1974
• Biology, Chemistry
• Journal of Pharmacy and Pharmacology

Previously we have shown that 3-chloroamphetamine has little effect on brain 5-hydroxytryptamine concentrations in rats because it is rapidly metabolized by ring hydroxylation, but if that route of metabolism is blocked, then 3-chloroamphetamine lowers brain 5-hydroxytryptamine concentrations as effectively as does 4-chloroamphetamine (Fuller, Schaffer & others, 1972). Those results were obtained at short times after the chloroamphetamines, and the duration of action of the drugs was not examined. More recently, it has been recognized that 4-chloroamphetamine depresses 5-hydroxytryptamine concentrations for several months after a single dose of the drug (Sanders-Bush, Bushing & Sulser, 1972). This prolonged lowering of brain 5-hydroxytryptamine concentrations (and of tryptophan hydroxylase activity and of 5-hydroxytryptamine uptake) may result from a neurotoxic action of 4-chloroamphetamine or a metabolite formed from it, since the duration resembles that of 5,6-dihydroxytryptamine or of 6-hydroxydopamine, agents that are toxic to 5-hydroxytryptamine and catecholamine neurons, respectively. We therefore wanted to know whether 3-chloroamphetamine shared with 4-chloroamphetamine the ability to cause long-lasting depletion of 5-hydroxyindole concentrations when their short-term effects were made essentially equal by blocking the rapid metabolism of the 3-chloro compound. Iprindole was chosen as the inhibitor of ring hydroxylation to avoid any effects on the neuional membrane pump that might occur with a hydroxylation inhibitor like desipramine (Freeman & Sulser, 1972). We also determined the possible influence of iprindole on the long-term depletion of 5-hydroxytryptamine by 4-chloroamphetamine, since conceivably a ring-hydroxylated metabolite could be responsible for the long-term effect of that drug. Reasons for considering such a possibility are (a) the long-lasting depletion of 5-hydroxytryptamine does not occur with the /?, @-difluoro derivative of 4-chloroamphetamine, which would not be expected to be ring hydroxylated (Fuller, Snoddy & Molloy, 1973) and (b) the long-lasting effect of 4-chloroamphetamine does not occur in mice, a species that is said not to ring hydroxylate amphetamines to nearly the extent that the rat does (Dring, Smith & Williams, 1970). Male albino rats of the Wistar strain, weighing about 150 g, received intraperitoneally saline or iprindole (10 mg kg-l) 1 h before 3-chloroamphetamine or 4-chloro-