title: alpha2-Adrenergic agonists antagonise the anxiolytic-like effect of antidepressants in the four-plate test in mice.
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 alpha(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 (0.03-0.5mg/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 alpha(2)-adrenoceptor agonists 30 min before the test, alpha(2)-adrenoceptor agonists failed to alter the anti-punishment effect of antidepressants. The results of this present study indicate that alpha(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.
authors.affiliation: Neurobiology of Anxiety and Depression, Faculty of Medicine, Nantes, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Massé
authors.forename: Martine
authors.initials: M
authors.lastname: Hascoët
authors.forename: Michel
authors.initials: M
authors.lastname: Bourin
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy*; D015283:Citalopram / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003511:Cyclohexanols / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003521:Cyclopropanes / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D006143:Guanabenz / Q000494:pharmacology; D008297:Male; D051379:Mice; D000078764:Milnacipran; D009043:Motor Activity / Q000187:drug effects; D017374:Paroxetine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011678:Punishment; D017367:Selective Serotonin Reuptake Inhibitors / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D000069470:Venlafaxine Hydrochloride
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000316:Adrenergic alpha-Agonists; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D015283:Citalopram; D003000:Clonidine; D003511:Cyclohexanols; D003521:Cyclopropanes; D006143:Guanabenz; D000078764:Milnacipran; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride