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

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 central alpha 1-adrenoceptors, attenuated an alpha 2-adrenoceptor-mediated response and inhibited a beta-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 central beta- and alpha 2-adrenoceptors and enhances the responsiveness of the central alpha 1-adrenoceptors with no apparent changes in the alpha 1-adrenoceptor density.