Time-dependent effects of antidepressant drugs on the low dose of apomorphine-induced locomotor hypoactivity in rats.

In the present study the hypothesis of antidepressant-induced subsensitivity of presynaptic dopamine receptors was readdressed. We used the behavioral model of low dose of apomorphine-induced locomotor hypoactivity in rats. Indeed, repeated administration of imipramine and citalopram attenuated the effect of low dose of apomorphine. However, the most interesting finding of the present study was the observation that similar and even stronger attenuation of low dose of apomorphine-induced hypoactivity was obtained by the acute treatment with imipramine, citalopram and amitriptyline, followed by 14 drug free days. That means that the acute antidepressant drug treatment seems to be sufficient to trigger the changes at the level of dopamine D2 presynaptic receptors and/or signal transduction mechanisms as a function of time, regardless of whether the drug is again administered. On the other hand, such the effect of time was not observed in the experiments using D-amphetamine as a motor stimulant. Only the repeated administration of antidepressant drugs enhanced the locomotor hyperactivity induced by D-amphetamine. Acute treatment, neither 2 h nor 14 days after the last dose, changed the D-amphetamine-induced hyperactivity. Such a difference in the time-dependent effects of antidepressant drugs on the locomotor activity induced by either the low dose of apomorphine or D-amphetamine may possibly result from the different mechanisms involved in the regulation of the biosynthesis of dopamine presynaptic and postsynaptic receptors in the rat brain.