Effect of the Serotonin Reuptake Inhibitor Fluoxetine on Pain Response in the Formalin Test, Stress System Reactivity, and Spatial Memory in Adult Rats.

The effect of chronic fluoxetine administration (versus saline control) on the behavioral biphasic pain response in the formalin test, hypothalamic-pituitary-adrenal (HPA) axis reactivity, spatial learning, and spatial memory was investigated in adult male rats. Following assessment of the pain response during both the first (acute) and second (tonic) phases of the formalin test, blood samples were collected from half of the experimental and control animals for measurement of plasma corticosterone levels. In the remaining rats, spatial learning and memory were evaluated in the Morris water maze. Chronic fluoxetine treatment produced a significant antinociceptive effect during the second inflammatory phase of the formalin test, which was accompanied by reduced HPA axis reactivity as evidenced by attenuated corticosterone responses. However, fluoxetine administration did not significantly affect performance in the cognitive domain.