, Volume 192, Issue 3, pp 357–371 | Cite as

Depletion of serotonin and catecholamines block the acute behavioral response to different classes of antidepressant drugs in the mouse tail suspension test

  • Olivia F. O’Leary
  • Anita J. Bechtholt
  • James J. Crowley
  • Tiffany E. Hill
  • Michelle E. Page
  • Irwin Lucki
Original Investigation



Few studies have investiga.ted whether the behavioral effects elicited by different types of antidepressant drugs are mediated by either serotonin (5-HT) or the catecholamines norepinephrine (NE) and dopamine (DA).


By depleting 5-HT, or NE and DA, the present study investigated the contributions of these monoamines to the acute behavioral effects of selective serotonin reuptake inhibitors (SSRIs; fluoxetine and citalopram) and norepinephrine reuptake inhibitors (NRIs; desipramine and reboxetine) in the mouse tail suspension test (TST).


Depletion of 5-HT tissue content by para-chlorophenylalanine (PCPA), an inhibitor of tryptophan hydroxylase, completely blocked reductions of immobility by the SSRIs in the TST. In contrast, PCPA did not alter the behavioral effects of the NRIs. Inhibition of catecholamine synthesis by α-methyl-para-tyrosine (AMPT) reduced brain NE and DA tissue content, whereas disruption of vesicular storage with reserpine decreased brain NE, DA and 5-HT tissue content. However, neither treatment completely prevented responses to desipramine, fluoxetine, or citalopram in the TST. Depleting both newly synthesized and vesicular components of NE and DA transmission with a combination of reserpine and AMPT completely prevented the behavioral effects of desipramine, reboxetine, and fluoxetine and attenuated those of citalopram. Although PCPA did not alter baseline immobility, AMPT and reserpine increased baseline values in the TST.


These studies demonstrated that endogenous 5-HT synthesis mediates the behavioral effects of SSRIs, but not NRIs, in the TST. In contrast, disruption of the behavioral effects of NRI and SSRI antidepressants required disruption of both catecholamine synthesis and vesicular storage and release mechanisms.


Antidepressant SSRI NRI Serotonin Norepinephrine Tail suspension test Behavior 



The authors gratefully acknowledge the assistance of Brad Hirsch in conducting parts of this study and Dr. John F. Cryan for helpful discussions. This research was supported by USPHS grants MH14654 and MH48125.


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Olivia F. O’Leary
    • 1
    • 3
  • Anita J. Bechtholt
    • 2
  • James J. Crowley
    • 1
  • Tiffany E. Hill
    • 2
  • Michelle E. Page
    • 4
  • Irwin Lucki
    • 1
    • 2
  1. 1.Department of PharmacologyUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of PsychiatryUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of PharmacologyNational University of Ireland, GalwayGalwayIreland
  4. 4.Department of Neurosurgery, Farber Institute of NeuroscienceThomas Jefferson UniversityPhiladelphiaUSA

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