_2-Adrenergic agonists antagonise the anxiolytic-like effect of antidepressants in the four-plate test in mice-

Authors
F. Massé, M. Hascoët, M. Bourin.

Lab
Faculty of Medicine, Neurobiology of Anxiety and Depression, Nantes, France

Journal
Behavioural Brain Research

Abstract
Selective serotonin reuptake inhibitors (SSRIs) and serotonin/noradrenaline reuptake inhibitors (SNRIs) has been reported to be efficient in anxiety disorders. Some animal models have demonstrated an anxiolytic-like effect following acute administration, however, it is not yet known how noradrenergic receptors are implicated in the therapeutic effects of antidepressants (ADs) in anxiety. The effects of two _2-adrenoceptor agonists (clonidine, guanabenz) on anxiolytic-like effect of two SSRIs (paroxetine and citalopram) and two SNRIs (venlafaxine and milnacipran) were evaluated in the four-plate test (FPT) in mice. Paroxetine (4 mg/kg), citalopram (8 mg/kg), venlafaxine (8 mg/kg), and milnacipran (8 mg/kg) administered intraperitoneally (i.p.) increased the number of punishments accepted by mice in the FPT. Clonidine (0.0039–0.5 mg/kg) and guanabenz (0.03–0.5 mg/kg) had no effect on the number of punishments accepted by mice. Clonidine (0.03 and 0.06 mg/kg) and guanabenz (0.125 and 0.5 mg/kg) (i.p. _45 min) reversed the anti-punishment effect of paroxetine, citalopram, venlafaxine and milnacipran (i.p. _30 min). But if the antidepressants are administered 45 min before the test and _2-adrenoceptor agonists 30 min before the test, _2-adrenoceptor agonists failed to alter the anti-punishment effect of antidepressants. The results of this present study indicate that _2-adrenoceptor agonists antagonise the anxiolytic-like effect of antidepressants in mice when they are administered 15 min before the administration of antidepressant suggesting a close inter-regulation between noradrenergic and serotoninergic system in the mechanism of SSRIs and SNRIs in anxiety-like behaviour.

BIOSEB Instruments Used:
Aron Test or Four Plates Test (LE830)