Some behavioural effects of antidepressant drugs are time-dependent.

1. The effects of repeated administration of antidepressant drugs (imipramine, IMI and citalopram, CIT) on the beta- and alpha2-adrenergic as well as dopaminergic D3 receptors were compared with time-dependent changes in the receptor responsiveness after acute treatment. 2. Repeated treatment with IMI or CIT (administered at a dose of 10 mg/kg p.o. twice a day for 14 days) induced down-regulation of beta-adrenergic receptors, demonstrated by behavioural experiment using salbutamol-induced hypoactivity and by binding studies using [3H]CGP12177. The changes in alpha2-adrenergic receptors were studied using clonidine-induced hypoactivity, which was attenuated by repeated treatment with IMI or CIT. Behavioural responsiveness of dopamine D3 receptors was investigated using two doses of 7-OH-DPAT. This drug at a dose of 0.05 mg/kg s.c. induced locomotor hypoactivity (interpreted as a result of stimulation of presynaptic dopamine D3 receptors), which was reversed by repeated administration of IMI or CIT, while 7-OH-DPAT at a dose of 3 mg/kg s.c. (which stimulated postsynaptic dopamine D3 receptors) induced significant hyperactivity, which was markedly enhanced by repeated administration of antidepressant drugs. 3. The effect of acute administration of IMI or CIT measured 14 days after drug treatment were similar to the described above alterations at the level of alpha2 adrenoreceptors and presynaptic dopamine D3 receptors, i.e. the drugs attenuated clonidine-induced hypoactivity and reversed locomotor hypoactivity evoked by low dose of 7-OH-DPAT. To induce the down-regulation of beta-adrenergic receptors or up-regulation of the behavioural responsiveness of dopaminergic D3 postsynaptic receptors, the repeated administration of IMI or CIT was necessary. 4. Therefore it has been concluded that presynaptic dopaminergic D3 and alpha2-adrenergic receptors are more sensitive to the acute treatment with antidepressant drugs than postsynaptic D3 and beta-adrenergic receptors.