A study of the possible influence of central 5-HT function on clonidine-induced hypoactivity responses in mice

Psychopharmacology (Berl). 1987;92(2):219-23. doi: 10.1007/BF00177919.


Administration of the alpha 2-adrenoceptor agonist clonidine (0.1 mg/kg) produces hypoactivity in mice. This sedation response was unaltered by pretreatment with either the 5-HT reuptake inhibitor zimeldine (1 or 10 mg/kg) or the 5-HT agonist quipazine (0.25 or 2.5 mg/kg). The 5-HT1B agonist RU 24969 (0.2 or 1 mg/kg) enhanced hypoactivity responses at the higher dose. The non-selective 5-HT antagonists methysergide (1 or 10 mg/kg) and metergoline (0.2 or 1 mg/kg) potentiated clonidine-induced hypoactivity. However, the marked enhancement produced by metergoline may have been due to its potent action as a alpha 1-adrenoceptor antagonist. Nevertheless, the 5-HT2 antagonists ritanserin (0.1 or 1 mg/kg) and ketanserin (0.1 or 1 mg/kg) both potentiated clonidine hypoactivity in a dose-dependent manner. beta-Adrenoceptor antagonists also inhibit 5-HT1 receptors at high dose. Pindolol (10 mg/kg) had no effect on sedation, but [-]-propranolol (20 mg/kg) caused some attenuation. This latter effect was probably not due to inhibition of 5-HT1 receptors, because this reduction also occurred at low dose (2 mg/kg). Destruction of 5-HT neurones by intracerebroventricular injection of 5,7-dihydroxytryptamine (50 micrograms) resulted in a marginal increase in hypoactivity. In conclusion, these data shown that central 5-HT function can influence alpha 2-adrenoceptor-mediated hypoactivity responses. However, since these effects were usually only apparent after severe manipulation of 5-HT function, it suggests that while these interactions may be of pharmacological interest, they are probably not of physiological importance.

MeSH terms

  • 5,7-Dihydroxytryptamine / pharmacology
  • Animals
  • Clonidine / pharmacology*
  • Depression, Chemical
  • Drug Interactions
  • Injections, Intraventricular
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects*
  • Neurons / drug effects
  • Neurons / physiology
  • Serotonin / physiology*
  • Serotonin Antagonists / pharmacology
  • Zimeldine / pharmacology


  • Serotonin Antagonists
  • 5,7-Dihydroxytryptamine
  • Serotonin
  • Zimeldine
  • Clonidine