Inhibition by venlafaxine of the increase in norepinephrine output in rat prefrontal cortex elicited by acute stress or by the anxiogenic drug FG 7142.
Venlafaxine is an antidepressant drug that inhibits the reuptake of serotonin and norepinephrine with different efficacies. The effects of repeated administration of this drug on the increase in the extracellular concentration of norepinephrine in the prefrontal cortex, induced by stress or by the anxiogenic drug FG 7142, were studied in freely moving rats. Exposure to foot-shock stress induced a marked increase (+120%) in the extracellular norepinephrine concentration in the prefrontal cortex of control rats. Long-term administration of venlafaxine (10 mg/kg i.p., once a day for 21 days) reduced the effect of stress on norepinephrine output by 75%. This effect of venlafaxine persisted for at least 5 days after discontinuation of drug treatment. Acute administration of FG 7142 (20 mg/kg i.p.), a benzodiazepine receptor inverse agonist, increased norepinephrine output (+90%) in control rats. Chronic treatment with venlafaxine prevented the effect of FG 7142. In contrast, the acute administration of this antidepressant had no effect on the stress- or FG 7142-induced increase in norepinephrine output. These plastic changes in the sensitivity of norepinephrine neurones to foot-shock stress and to an anxiogenic drug may reveal an important neuronal mechanism for the physiological regulation of emotional state. Furthermore, this mechanism might be relevant to the anxiolytic and antidepressant effects of venlafaxine.
Dazzi
Laura
L
Department of Experimental Biology B. Loddo, University of Cagliari, Italy. dazzi@unica.it
Vignone
Vincenzo
V
Seu
Emanuele
E
Ladu
Stefania
S
Vacca
Giada
G
Biggio
Giovanni
G
D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism* / Q000523:psychology; D002243:Carbolines / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013315:Stress, Psychological / Q000378:metabolism*; D000069470:Venlafaxine Hydrochloride
D002243:Carbolines; D003511:Cyclohexanols; D018755:GABA Agonists; D009638:Norepinephrine; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride; C035874:FG 7142