Conclusions
Acute administration of hormones blocked the effects of DMI (given three times over 24 h) in the FST. However, chronic administration of these hormones failed to block the effects of chronically administered DMI (at a dose that produces clinically relevant serum concentrations).
Results
In the acute study, the hormones blocked the effects of DMI in the FST as demonstrated by the absence of either a reduction in immobility or an increase in climbing behavior in animals treated with DMI in combination with the hormones. Concentration-response experiments on hippocampal synaptosomes revealed no changes in the Km or Bmax for uptake of (3)H-NE in hormone-treated rats. In the chronic study, the antidepressant-like effects of DMI in the FST were not blocked by chronic administration of hormones. Interestingly, the hormones affected the serum concentrations of DMI. These levels were significantly higher in animals receiving 10 or 15 mg/kg/day in hormone-treated rats as compared to those with placebo. Conclusions: Acute administration of hormones blocked the effects of DMI (given three times over 24 h) in the FST. However, chronic administration of these hormones failed to block the effects of chronically administered DMI (at a dose that produces clinically relevant serum concentrations).