5-Hydroxytryptamine1A (5-HT1A) receptors have been shown to be suppressed by corticosteroid hormones in a variety of animal experimental paradigms. It has been suggested that this effect may be central to the pathophysiology of severe clinical depressive illness, a condition in which 5-HT1A receptor function is reduced and corticosteroid hormones are elevated. We report the effects of acute administration of hydrocortisone in normal volunteers on a neuroendocrine model of 5-HT1A receptor function. Fifteen healthy male volunteers took part in a random order, double blind, placebo controlled study, in which 100 mg hydrocortisone or placebo was administered 11 h before infusion of L-tryptophan (L-TRP). Pre-treatment with hydrocortisone significantly reduced the growth hormone (GH), but not the prolactin (PRL) response to the infusion. These data are consistent with the view that acute administration of corticosteroid hormones significantly impairs 5-HT1A receptor mediated function in healthy human volunteers and are in line with animal studies of the effects of corticosteroid hormones on 5-HT1A receptors. We propose that this finding is relevant to the pathophysiological processes which cause severe depressive illness.

SUMMARY

These data contrast with a previous study using hydrocortisone in the same paradigm and demonstrate important functional differences between dexamethasone and hydrocortisone.

Interactions between the 5-HT system and the dopaminergic system and cholinergic system may be important in determining cognitive function and motor function in Parkinson's disease (PD). Previous studies have shown effects of reducing serotonin function, by acute tryptophan depletion (ATD), on neuropsychological function. In particular, an adverse effect on verbal memory has been demonstrated. This study compared with the effects of ATD on cognitive and motor function in PD and healthy control subjects. The effects of ATD were investigated in a double-blind, placebo-controlled, counterbalanced, cross-over, randomised design in 20 patients with PD and 35 healthy controls matched for age, gender and premorbid IQ. There was a differential group effect of ATD on global cognitive function whereby the mean score on the modified mini mental state examination during ATD was lower than placebo in PD but higher in controls. There was a similar pattern of effects on verbal recognition. In a visual recognition task, ATD improved performance in the PD but not in the control group. In terms of psychomotor speed, there was also a group-specific effect with reduced latency of response during ATD in the PD group but increased latency in the control group. ATD has subtle neuropsychological effects, which differ significantly between PD and healthy control subjects. This suggests that the dopaminergic and cholinergic deficit of PD significantly modulates the effects of serotonin depletion, resulting in positive effects in some domains. Further investigation on the effects of specific serotonin antagonists may be merited in PD.

The data suggest enhancement of transmission through postsynaptic 5-HT(1A) receptors by venlafaxine but not paroxetine, after only 3 h.