Journal of psychopharmacology
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J. Psychopharmacol. (Oxford) · Jun 2002
Effect of chronic fluoxetine and WAY-100635 treatment on serotonergic neurotransmission in the frontal cortex.
Clinical augmentation strategies have shown that some improvement in antidepressant efficacy can be achieved by combining the beta-adrenergic/serotonin (5-HT)1A/1B receptor antagonist (+/-)pindolol with a selective serotonin reuptake inhibitor (SSRI). This has lead to the hypothesis that a combination of a 5-HT1A receptor antagonist with an SSRI will lead to a faster onset of antidepressant action. Although there is a significant accumulation of acute preclinical data supporting this rationale, until recently, there have been no investigations examining the chronic effects of combining an SSRI with a 5-HT1A receptor antagonist. ⋯ WAY-100635 given chronically in combination with fluoxetine blocked the SSRI-induced desensitization of the 5-HT1A receptor. Furthermore, chronic treatment with this combination produced no tolerance in terms of its ability to acutely increase forebrain 5-HT levels. These data suggest that augmentation of an SSRI by combined pharmacotherapy with a 5-HT1A antagonist would be effective upon prolonged exposure.