Tricyclic antidepressants vary in decreasing alpha 2-adrenoceptor sensitivity with chronic treatment: assessment with clonidine inhibition of acoustic startle

Br J Pharmacol. 1982 Oct;77(2):217-22. doi: 10.1111/j.1476-5381.1982.tb09288.x.


1 Clonidine inhibition of the acoustic startle reflex in the rat was used as a behavioural measure of alpha 2-adrenoceptor sensitivity following acute or chronic administration of tricyclic antidepressants. 2 Chronic (14 day) administration of desipramine (10 mg/kg, i.p.) attenuated the depressant effect of clonidine (20 or 40 microgram/kg) on the startle reflex. 3 No change in response to clonidine was obtained after chronic treatment with two other tricyclic antidepressants, amitriptyline (10 mg/kg) or iprindole (5 mg/kg). 4 Acute administration of these tricyclics (1 h) did not modify the effect of clonidine on startle. 5 It is suggested that the development of alpha 2-adrenoceptor subsensitivity produced by chronic tricyclics may be unique to those compounds, such as desipramine, which are active in blocking the uptake of noradrenaline.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antidepressive Agents, Tricyclic / pharmacology*
  • Clonidine / pharmacology*
  • Desipramine / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Male
  • Rats
  • Receptors, Adrenergic / drug effects*
  • Receptors, Adrenergic, alpha / drug effects*
  • Reflex, Startle / drug effects*
  • Time Factors


  • Antidepressive Agents, Tricyclic
  • Receptors, Adrenergic
  • Receptors, Adrenergic, alpha
  • Clonidine
  • Desipramine