Abstract
Immobility scores in the swimming test and brain concentrations of desipramine were determined in rats and mice following repeated injection of the antidepressant versus acute administration of either a behaviorally effective or ineffective dose of the drug. Five injections (IP) of desipramine (each injection being performed at the measured T1/2 of the drug in the brain) reduced immobility scores by 30%, whereas this regimen resulted in brain drug concentrations not different from those obtained after a single, behaviorally ineffective dose of desipramine. It is suggested that the enhanced “antidepressant” response such as that frequently observed in animals after repeated injection of imipramine-like drugs does not involve accumulation of the drug in the brain.
This is a preview of subscription content, log in via an institution to check access.
References
Amsterdam J, Brunswick D, Mendels J (1980) The clinical application of tricyclic antidepressant pharmacokinetics and plasma levels. Am J Psychiatry 137:653–661
Breyer-Pfaff U, Spribille T, Jahns I (1978) Influence of phenobarbital on the distribution and elimination of desmethylimipramine in the rat. Biochem Pharmacol 22:1521–1526
Dingell JV, Sulser F, Gillette JR (1964) Species differences in the metabolism of imipramine and desmethylimipramine (DMI). J Pharmacol Exp Ther 143:14–22
Diquet B, Gaudel G, Colin JN (1983) Dosage de la désipramine par chromatographie liquide à haute performance dans le sang et le cerveau de souris. Ann Pharmaceutiques Françaises 41:269–274
Duncan GE, Paul IA, Harden TK, Mueller RA, Stumpf WE, Breese GR (1985) Rapid dow regulation of beta-adrenergic receptors by combining antidepressant drugs with forced swim: a model of antidepressant-induced neural adaptation. J Pharmacol Exp Ther 234:402–408
Kitada Y, Miyauchi T, Satoh A, Satoh S (1981) Effects of antidepressants in the rat forced swimming test. Eur J Pharmacol 72:145–152
Pollock BG, Perel JM, Shostak M (1985) Rapid achievement of antidepressant effect with intravenous chlorimipramine. N Engl J Med 312:1130
Porsolt RD, Bertin A, Jalfre M (1978) Behavioural despair in rats and mice: Strain differences and the effects of imipramine. Eur J Pharmacol 51:291–294
Quitkin FM (1985) The importance of dosage in prescribing antidepressants. Br J Psychiatry 147:593–597
Reisine TD (1981) Adaptative changes in catecholamine receptors in the central nervous system. Neuroscience 6:1471–1502
Sherman AD, Sacquitne JL, Petty F (1982) Specificity of the learned helplessness model of depression. Pharmacol Biochem Behav 16:449–454
Szymura-Olesksiak J, Panas M, Chrusciel W (1984) The distribution of imipramine and desipramine in rat brain regions after single and chronic administration of imipramine. Pol J Pharmacol Pharm 36:21–26
Sugrue MF (1983) Chronic antidepressant therapy and associated changes in central monoaminergic receptor functioning. Pharmacol Ther 21:1–33
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Poncelet, M., Gaudel, G., Danti, S. et al. Acute versus repeated administration of desipramine in rats and mice: Relationships between brain concentrations and reduction of immobility in the swimming test. Psychopharmacology 90, 139–141 (1986). https://doi.org/10.1007/BF00172885
Issue Date:
DOI: https://doi.org/10.1007/BF00172885