Modification of central serotonergic and dopaminergic behaviors in the course of chronic corticosteroid administration

The effect of chronic cortisol administration (12.5 mg/kg per day p.o.) was studied in guinea pigs using two behavioral models; apomorphine-induced stereotypy (SB) and 1-5-HTP-induced myoclonus (MJB). Diurnal variations in behavioral sensitivity were evaluated by behavioral testing at five time points over a 24 h period at bi-weekly intervals. Cortisol succinate administration suppresses 1-5-HTP myoclonus in all animals and abolishes diurnal fluctuations in sensitivity during the first two weeks of therapy. At four weeks, a subgroup is observed which is behaviorally hypersensitive to 1-5-HTP. These changes occur in association with a reduction in the behavioral response to apomorphine but in the absence of major disruption in diurnal behavioral threshold variation to apomorphine. Chronic cortisol administration appears to induce major alterations in central serotonin-mediated behaviors. This observation may explain the therapeutic effect of corticosteroids in certain forms of myoclonus and the role of cortisol rhythm disturbances in the context of a variety of psychiatric disorders.