TRICYCLIC ANTIDEPRESSANTS VARY IN DECREASING α‐ADRENOCEPTOR SENSITIVITY WITH CHRONIC TREATMENT: ASSESSMENT WITH CLONIDINE INHIBITION OF ACOUSTIC STARTLE

Abstract

Clonidine inhibition of the acoustic startle reflex in the rat was used as a behavioural measure of α2‐adrenoceptor sensitivity following acute or chronic administration of tricyclic antidepressants. Chronic (14 day) administration of desipramine (10 mg/kg, i.p.) attenuated the depressant effect of clonidine (20 or 40 Mg/kg) on the startle reflex. 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). Acute administration of these tricyclics (1 h) did not modify the effect of clonidine on startle. It is suggested that the development of α2‐adrenoceptor subsensitivity produced by chronic tricyclics may be unique to those compounds, such as desipramine, which are active in blocking the uptake of noradrenaline. 1982 British Pharmacological Society