Chronic treatment with the potential antidepressant drug rolipram: the effect on the behavioural responses to adrenergic and dopaminergic receptor agonists with some biochemical correlates

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Abstract
We studied the effect of acute and chronic treatment with rolipram, a potential antidepressant drug, on the behavioural responses induced by adrenergic and dopaminergic receptor agonists in mice and rats, and on (3H)prazosin and (3H)dihydroalprenolol binding to cortical membranes and whole brain noradrenaline and dopamine utilization in rats. Chronic, but not acute, administration of rolipram potentiated a behavioural response mediated through centralα1-adrenoceptors, attenuated anα2-adrenoceptormediated response and inhibited aβ-adrenoceptor-mediated response. Neither treatment affected the behavioural responses to dopaminergic stimulants. Repeated treatment with rolipram decreased the density of cortical (3H)dihydroalprenolol, but not (3H)prazosin bindings sites, and reduced brain noradrenaline, but not dopamine utilization. These results suggest that chronic administration of rolipram induces the down-regulation of the centralβ- andα2-adrenoceptors and enhances the responsiveness of the centralα1-adrenoceptors with no apparent changes in theα1-adrenoceptor density.