title: Chronic treatment with imipramine or mirtazapine antagonizes stress- and FG7142-induced increase in cortical norepinephrine output in freely moving rats.
abstract: The effect of repeated administration of imipramine or mirtazapine, two antidepressant drugs with different mechanisms of action, was studied on the stress-induced increase in the extracellular concentration of norepinephrine in the prefrontal cortex of freely moving rats. Exposure to footshock in control rats induced a marked increase in extracellular norepinephrine concentrations in the prefrontal cortex (+120%). Long-term administration with imipramine or mirtazapine (10 mg/kg, i.p., twice or once a day, respectively, for 14 days) reduced (+50%) the effect of stress on basal norepinephrine output. Acute administration of FG7142 (30 mg/kg, i.p.), an anxiogenic benzodiazepine receptor inverse agonist, induced a marked increase in norepinephrine output (+90%) in control rats. In rats chronically treated with imipramine or mirtazapine this effect was completely antagonized. On the contrary, acute administration of these antidepressant drugs failed to reduce stress- and FG7142-induced increase in norepinephrine output. The plastic changes in the sensitivity of norepinephrine neurons to footshock stress and drug-induced anxiogenic stimuli may reveal a new important neuronal mechanism involved in the long-term modulation of emotional state. This action might be relevant for the anxiolytic and antidepressant effect of antidepressant drugs.
authors.affiliation: Department of Experimental Biology "B. Loddo," Chair of Pharmacology, University of Cagliari, Cagliari, Italy. dazzi@vaxca1.unica.it
authors.forename: Laura
authors.initials: L
authors.lastname: Dazzi
authors.forename: Stefania
authors.initials: S
authors.lastname: Ladu
authors.forename: Francesca
authors.initials: F
authors.lastname: Spiga
authors.forename: Giada
authors.initials: G
authors.lastname: Vacca
authors.forename: Antonella
authors.initials: A
authors.lastname: Rivano
authors.forename: Luigi
authors.initials: L
authors.lastname: Pira
authors.forename: Giovanni
authors.initials: G
authors.lastname: Biggio
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D002243:Carbolines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D018756:GABA Antagonists / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000078785:Mirtazapine; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D013312:Stress, Physiological / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D000929:Antidepressive Agents, Tricyclic; D002243:Carbolines; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D008803:Mianserin; C035874:FG 7142; D000078785:Mirtazapine; D007099:Imipramine; D009638:Norepinephrine