Repeated Treatment with Antidepressant Drugs: Responses Mediated by Brain Dopamine Receptors


The therapeutic effect of antidepressant drugs (AD) in patients appears after about two weeks of treatment, and not immediately after the administration of a single dose. Such a latency period is observed for virtually all AD and is independent of the mechanism of action in the acute experiment. Therefore, it is justifiable to study the mechanism of antidepressant action in animals treated repeatedly with these drugs. In past years, the pharmacological and biochemical effects of repeated (not single-dose) administration of AD have been described in relation to a number of neurotransmitter systems or receptors (see Charney et al. 1981; Maj et al. 1984a). We have recently concentrated upon studying the effect of AD, given repeatedly, on the dopamine brain systems; this relationship has not yet been sufficiently examined (see Discussion). We used typical and atypical AD with different profiles revealed in the acute experiment, given, as a rule, in a dose of 10 mg/kg per orally, twice a day for 14 days. Pharmacological responses considered to be mediated by dopamine brain receptors — locomotor activity, exploratory behavior, stereotypy — were studied. Biochemical experiments (binding to dopamine receptors, levels of dopamine and its metabolites) were also carried out. The results of these studies are reviewed in this paper.


Locomotor Activity Dopamine Receptor Nucleus Accumbens Antidepressant Drug Repeated Treatment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Antkiewicz-Michaluk L, Rokosz-Pelc A, Vetulani J (to be published) Increased low-affinity 3H-spiroperidol binding to rat cortical membranes after chronic antidepressant treatments. Pol J Pharmacol Pharm 37.Google Scholar
  2. Arnt J, Hyttel J, Fredricson Overo K (1984) Prolonged treatment with the specific 5-HT-uptake inhibitor citalopram: effect on dopaminergic and serotonergic functions. Pol J Pharmacol Pharm 36:221–230.PubMedGoogle Scholar
  3. Charney DS, Menkes DB, Heninger GR (1981) Receptor sensitivity and the mechanism of action of antidepressant treatment. Arch Gen Psychiatry 38:1160–1180.PubMedGoogle Scholar
  4. Delini-Stula A, Vassout A (1979) Modulation of dopamine-mediated behavioural responses by antidepressants. Effects of single and repeated treatment. Eur J Pharmacol 58:443–451.PubMedCrossRefGoogle Scholar
  5. Enna SJ, Mann E, Kendall D, Stancel GM (1981) Effect of chronic antidepressant administration of brain neurotransmitter receptor binding. In: Enna SJ, Malick JB, Richelson E (eds) Antidepressants: neurochemical, behavioural, and clinical perspectives. Raven, New York, pp 91–105.Google Scholar
  6. Maj J (1984) Mechanism of action of antidepressant drugs given repeatedly: changes in the responses mediated by noradrenaline (α1) and dopamine receptors. In: Paton W, Mitchell J, Turner P (eds) IUPHAR 9th International Congress of Pharmacologgy, July 29–August 4, 1984, London, proceedings, vol 3. Macmillan, London, pp 137–143.Google Scholar
  7. Maj J, Wędzony K (1985) The repeated treatment with imipramine and amitriptyline increases the locomotor response tod-amphetamine given into the nucleus accumbens. J Pharm Pharmacol 37:362–364.PubMedCrossRefGoogle Scholar
  8. Maj J, Mogilnicka E, Kordecka A (1979) Chronic treatment with antidepressant drugs: potentiation of apomorphine-induced aggressive behaviour in rats. Neurosci Lett 13:337–341.PubMedCrossRefGoogle Scholar
  9. Maj J, PrzegaliĔski E, Mogilnicka E (1984a) Hypotheses concerning the mechanism of action of antidepressant drugs. In: Adrian RH, zur Hausen H, Helmreich E, Holzer H, Jung R, Linden RJ, Miescher PA, Piiper J, Rasmussen H, Trendelenburg U, Ullrich K, Vogt W, Weber A (eds) Reviews of physiology, biochemistry and pharmacology, vol 100. Springer, Berlin Heidelberg New York Tokyo, pp 1–74.Google Scholar
  10. Maj J, Rogóź Z, Skuza G, SowiĔska H (1984b) Repeated treatment with antidepressant drugs potentiates the locomotor response to (+)-amphetamine. J Pharm Pharmacol 36:127–130.PubMedCrossRefGoogle Scholar
  11. Maj J, Rogóź Z, Skuza G, SowiĔska H (1984 c) Repeated treatment with antidepressant drugs increases the behavioural response to apomorphine. J Neural Transm, in press.Google Scholar
  12. Maj J, Rogóź Z, Skuza G, SowiĔska H (1985) The effects of repeated treatment with antidepressant drugs on the action of D-amphetamine and apomorphine in rats. In: Kelemen K, Magyar K, Vizi ES (eds) Neuropharmacology 1985. Publishing House of the Hungarian Academy of Sciences, Budapest, pp 133–139.Google Scholar
  13. Martin-Iverson MT, Leclere JF, Fibiger HC (1983) Cholinergic-dopaminergic interactions and mechanisms of action of antidepressants. Eur J Pharmacol 94:193–201.PubMedCrossRefGoogle Scholar
  14. Neal H, Bradley PB (1979) Electrocortical changes in the encephalé isolé cat following chronic treatment with antidepressant drugs. Neuropharmacology 18:611–615.PubMedCrossRefGoogle Scholar
  15. Pijnenburg AJJ, Honig WMM, van der Heyden JAM, Van Rossum JM (1976) Effects of chemical stimulation of the mesolimbic dopamine system upon locomotor activity. Eur J Pharmacol 35:45–58.PubMedCrossRefGoogle Scholar
  16. Smiatowski A, Maj J (1985) Repeated treatment with imipramine potentiates the locomotor effect of apomorphine administered into hippocampus. Psychopharmacology, in press.Google Scholar
  17. Spyraki C, Fibiger HC (1981) Behavioural evidence for supersensitivity of postsynaptic dopamine receptors in the mesolimbic system after chronic administration of desipramine. Eur J Pharmacol 74:195–206.PubMedCrossRefGoogle Scholar
  18. Sugrue MP (1981) Current concepts in the mechanism of action of antidepressant drugs. Pharmacol Ther 13:219–247.PubMedCrossRefGoogle Scholar
  19. Wędzony K, Maj J (1983) The effect of repeated treatment with imipramine on the locomotor hyperactivity induced in rats by amphetamine administered into the nucleus accumbens. 8th Congress of the Polish Pharmacological Society, 26–28 September 1983. Warsaw, Abstracts, Poster 181.Google Scholar
  20. Willner P (1983) Dopamine depression: a review of recent evidence. III. The effects of antidepressant treatments. Brain Res Rev 6:237–246.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • J. Maj
    • 1
  1. 1.Institute of PharmacologyPolish Academy of SciencesKrakówPoland

Personalised recommendations