Neuroanatomical substrates involved in the anxiogenic-like effect of acute fluoxetine treatment.
An initial exacerbation of anxiety can be observed in animals and humans treated with selective serotonin reuptake inhibitors (SSRIs). The neurobiological substrates and mechanism(s) underlying this effect are not clear. We used Fos expression as a marker of neuronal activation to investigate effects of acute fluoxetine treatment in rats submitted to two different models of emotional stress, airjet and immobilization. Exposure to both stressors induced Fos expression in various brain regions implicated in fear/anxiety mechanisms. Acute treatment with 5 mg/kg fluoxetine facilitated airjet-induced escape responses and enhanced the airjet-, as well as immobilization-induced Fos expression exclusively in the locus coeruleus (LC), but not in other areas including the amygdala, hypothalamus or septum. Fluoxetine also facilitated airjet-induced noradrenaline efflux in the medial prefrontal cortex, a projection area of LC noradrenergic neurons. A higher dose of fluoxetine (10 mg/kg) did not change escape responses and had no effect on stress-induced Fos expression in the LC, but decreased airjet-induced Fos expression in the medial amygdala. The results indicate that anxiogenic effects of acute fluoxetine treatment occur in a specific dose range and can be mimicked by exacerbation of escape responses in the airjet model. Furthermore, facilitation of escape responses by fluoxetine is linked to enhanced activity in the LC/noradrenaline system.
Salchner
Peter
P
Department of Pharmacology and Toxicology, University of Innsbruck, Peter-Mayr- Strasse 1, A-6020, Innsbruck, Austria.
Singewald
Nicolas
N
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology; D005473:Fluoxetine / Q000008:administration & dosage*; D016762:Genes, fos / Q000187:drug effects / Q000502:physiology; D007103:Immobilization / Q000502:physiology; D007398:Interpersonal Relations; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000188:drug therapy / Q000378:metabolism
D014151:Anti-Anxiety Agents; D005473:Fluoxetine; D009638:Norepinephrine