, Volume 115, Issue 4, pp 441–446 | Cite as

Parallel changes in dopamine D2 receptor binding in limbic forebrain associated with chronic mild stress-induced anhedonia and its reversal by imipramine

  • Mariusz Papp
  • Violetta Klimek
  • Paul Willner
Original Investigations


Chronic sequential exposure to a variety of mild stressors has previously been found to cause an antidepressant-reversible decrease in the consumption of palatable sweet solutions, associated with abnormalities of dopaminergic neurotransmission in the nucleus accumbens. In the present study, 5 weeks of treatment with imipramine (10 mg/kg b.i.d.) reversed the decreased sucrose intake of rats exposed to chronic mild stress. Stress also caused a decrease in D2-receptor binding in the limbic forebrain (but not the striatum), which was completely reversed by imipramine. In nonstressed animals, imipramine decreased D1-receptor binding in both regions. However, in stressed animals, imipramine did not significantly alter D1-receptor binding in either area. Stress alone slightly increased D1-receptor binding, in striatum only. Scatchard analysis showed that all changes in receptor binding resulted from changes in receptor number (Bmax) rather than receptor affinity (KD). The results support the hypothesis that changes in D2-receptor function in the nucleus accumbens are responsible for chronic mild stress-induced anhedonia and its reversal by antidepressant drugs. They do not support the hypothesis that the sensitization of D2-receptors seen following chronic antidepressant treatment is caused by a down-regulation of D1-receptors.

Key words

Chronic mild stress Imipramine Animal model of depression Dopamine D1-receptors D2-receptors Rat 


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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Mariusz Papp
    • 1
  • Violetta Klimek
    • 1
  • Paul Willner
    • 2
  1. 1.Institute of Pharmacology, Polish Academy of SciencesKrakowPoland
  2. 2.Department of PsychologyUniversity of WalesSwansea, Singleton ParkUK

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