Some behavioural effects of antidepressant drugs are time-dependent

1. The effects of repeated administration of antidepressant drugs (imiprami ne, IMI and citalopram, CIT) on the beta- and alpha (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 beta -adrenergic re ceptors, demonstrated by behavioural experiment using salbutamol-induced hy poactivity and by binding studies using [H-3]CGP12177. The changes in alpha (2)-adrenergic receptors were studied using clonidine-induced hypoactivity , which was attenuated by repeated treatment with IMI or CIT. Behavioural r esponsiveness 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 hypoac tivity (interpreted as a result of stimulation of presynaptic dopamine D-3 receptors), which was reversed by repeated administration of TMI or CIT, wh ile 7-OH-DPAT at a dose of 3 mg/kg s.c. (which stimulated postsynaptic dopa mine D-3 receptors) induced significant hyperactivity, which was markedly e nhanced 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 at adrenoreceptors and presynaptic dopamine D-3 receptors, i.e. the dru gs attenuated clonidine-induced hypoactivity and reversed locomotor hypoact ivity evoked by low dose of 7-OH-DPAT. To induce the down-regulation of bet a -adrenergic receptors or up-regulation of the behavioural responsiveness of dopaminergic D-3 postsynaptic receptors the repeated administration of I MI or CIT was necessary. 4. Therefore it has been concluded that presynaptic dopaminergic D-3 and al pha (2)-adrenergic receptors are more sensitive to the acute treatment with antidepressant drugs than postsynaptic D-3 and beta -adrenergic receptors.