Some behavioural effects of antidepressant drugs are time-dependent

Abstract 1. The effects of repeated administration of antidepressant drugs (imipramine, IMI and citalopram, CIT) on the β- and α 2 -adrenergic as well as dopaminergic D 3 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 β-adrenergic receptors, demonstrated by behavioural experiment using salbutamol-induced hypoactivity and by binding studies using [ 3 H]CGP12177. The changes in α 2 -adrenergic receptors were studied using clonidine-induced hypoactivity, which was attenuated by repeated treatment with IMI or CIT. Behavioural responsiveness of dopamine D 3 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 D 3 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 D 3 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 α 2 adrenoreceptors and presynaptic dopamine D 3 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 β-adrenergic receptors or up-regulation of the behavioural responsiveness of dopaminergic D 3 postsynaptic receptors, the repeated administration of IMI or CIT was necessary. 4. Therefore it has been concluded that presynaptic dopaminergic D 3 and α 2 -adrenergic receptors are more sensitive to the acute treatment with antidepressant drugs than postsynaptic D 3 and β-adrenergic receptors.