Clonidine potentiates the effects of 5-HT1A, 5-HT1B and 5-HT2A/2C antagonists and 8-OH-DPAT in the mouse forced swimming test

Eur Neuropsychopharmacol. 1998 Aug;8(3):169-73. doi: 10.1016/s0924-977x(97)00073-4.


The present study was undertaken to identify the receptor subtypes involved in clonidine's ability to enhance the effects of antidepressant drugs in the mouse forced swimming test. Clonidine (0.06 mg/kg, i.p.) significantly enhanced the antidepressant-like effects of subactive doses of the 5-HT1A receptor agonist, 8-OH-DPAT (1 mg/kg, i.p.; P<0.01); the 5-HT1A receptor antagonist, NAN 190 (0.5 mg/kg, i.p.; P<0.01); the 5-HT1A/1B autoreceptor antagonist, (+/-) pindolol (32 mg/kg, i.p.; P<0.01); the 5-HT2A/2C receptor antagonist, ritanserin (4 mg/kg, i.p.; P<0.01). Pretreatment with clonidine failed to increase mobility when administered in combination with the 5-HT1B receptor agonist, RU 24969 (1 mg/kg, i.p.) or the 5-HT2A receptor antagonist, ketanserin (8 mg/kg, i.p.). In conclusion, clonidine-induced anti-immobility effects are more likely mediated by 5-HT1A and 5-HT2C receptors, as well as alpha-2-adrenergic autoreceptors situated on noradrenergic neurones. The results of the present study also demonstrate that serotonergic receptor function can influence alpha-2-adrenoreceptor mediated responses in the mouse forced swimming test.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / antagonists & inhibitors
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Clonidine / pharmacology*
  • Male
  • Mice
  • Serotonin Antagonists / metabolism*
  • Serotonin Antagonists / pharmacology*
  • Serotonin Receptor Agonists / metabolism
  • Serotonin Receptor Agonists / pharmacology
  • Swimming / physiology
  • Swimming / psychology


  • Antihypertensive Agents
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Clonidine