EFFECT OF PAROXETINE AND NEFAZODONE ON 5 H1A RECEPTOR SENSITIVITY

Animal experimental studies suggest that the therapeutic effect of sel ective serotonin re-uptake inhibitors (SSRIs) may involve neuroadaptiv e changes in pre- and post-synaptic serotonin(1A) (5-HT1A) receptors. We used the endocrine and hypothermic responses to the 5-HT1A receptor agonist, gepirone (20 mg orally), to assess 5-HT1A receptor sensitivi ty in 37 healthy male volunteers who were studied before and following random double-blind, allocation to treatment with paroxetine, nefazod one or placebo for 17 days. Following antidepressant drug treatment, h ypothermic responses to gepirone were markedly decreased by paroxetine but only slightly diminished by nefazodone. Paroxetine also lowered t he growth hormone and cortisol responses to gepirone. There nas no cha nge in either hypothermic or endocrine response following placebo trea tment. Our results suggest that paroxetine treatment produces a striki ng attenuation of measures of both pre-and post-synaptic 5-HT1A recept or function. Nefazodone appears to decrease the sensitivity of 5-HT1A autoreceptors to some extent and this effect may contribute to its ant idepressant activity.