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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 302, Issue 1, pp 115–118 | Cite as

Attenuated feed-back inhibition of brain serotonin synthesis following chronic administration of imipramine

  • Torgny H. Svensson
Article

Summary

Acute administration of imipramine (IMI), 15 mg/kg i.p., significantly reduced the accumulation of 5-hydroxytryptophan (5-HTP) in various parts of the rat brain during 30 min following treatment with NSD 1015, 100 mg/kg i.p., and inhibitor ofl-aromatic amino acid decarboxylase. The simultaneously measured accumulation of 3,4-dihydroxyphenylalanine (Dopa) was increased in the dopamine (DA) dominated brain parts but, if anything, slightly reduced (10%) in the noradrenaline (NA) rich hemispheres. Twelve hours after cessation of a chronic IMI-regimen (10 mg/kg i.p., 12 h intervals, 14 days), the 5-HTP- and Dopa-accumulations in the various brain parts were not different from those in saline-treated controls. However, when IMI, 15 mg/kg i.p., was administered to the chronically IMI-treated rats, 12h after the last injection, no significant reduction in 5-HTP accumulation was obtained in any of the brain parts analyzed (limbic system, corpus striatum, hemispheres and brain stem). In the NA-rich brain parts, there was no reduction in the Dopa accumulation, whereas in the DA-dominated regions the same increase in Dopa accumulation was seen as when IMI, 15 mg/kg, was given to naive rats. In conclusion, the data show that the feed-back inhibition of central 5-hydroxytryptamine (5-HT) synthesis by IMI is attenuated by chronic IMI treatment.

Key words

Imipramine Monoamine synthesis Feed-back inhibition Chronic administration 

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Copyright information

© Springer-Verlag 1978

Authors and Affiliations

  • Torgny H. Svensson
    • 1
  1. 1.Department of PharmacologyUniversity of GöteborgGöteborgSweden

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