Effect of long-term administration of antidepressant treatments on serotonin release in brain regions involved in obsessive–compulsive disorder

Background: Among all antidepressant treatments, including electroconvulsive shock (ECS) therapy and monoamine oxidase inhibitors (MAOIs), only the selective serotonin (5-HT) reuptake inhibitors (SSRIs) exert a clear therapeutic effect in obsessive–compulsive disorder (OCD). An 8-week, but not a 3-week treatment with the SSRI paroxetine results in an increased electrically evoked [3H]5-HT release and a desensitization of 5-HT autoreceptors in the guinea pig orbitofrontal cortex, a brain region implicated in OCD. Methods: In the present study, the effect of long-term treatment with the SSRI fluoxetine, ECS, and the reversible type A MAOI moclobemide was investigated on evoked [3H]5-HT release from preloaded guinea pig brain slices prepared from the hypothalamus, cingulate cortex, and orbitofrontal cortex. Results: Fluoxetine treatment yielded an enhanced [3H]5-HT release in the three brain areas, but a desensitization of the 5-HT autoreceptor only in the hypothalamus and orbitofrontal cortex. ECS treatment did not result in any alteration of the electrically evoked [3H]5-HT release or of 5-HT autoreceptor sensitivity in any of the brain regions. Moclobemide increased [3H]5-HT release only in the orbitofrontal cortex without any alteration in the 5-HT autoreceptor sensitivity. Conclusions: These findings indicate that only treatments effective in OCD have the capacity to desensitize the terminal 5-HT autoreceptor in the orbitofrontal cortex.