Treatment with antidepressants and histamine receptor mediated 3H-cyclic AMP formation in guinea pig cortex

It has been recently reported that most of the antidepressant drugs block histamine H1 and H2 receptors in the brain under in vitro conditions and it has been suggested that this may be related in part to their therapeutic effect. Since the in vitro and in vivo effects of these drugs may differ, we studied the effect of treatment with antidepressant drugs on histamine receptor sensitivity in the guinea pig brain and observed that chronic treatment with tricyclic antidepressants or phenelzine (an MAO inhibitor) causes a reduction in histamine receptor sensitivity. This reduction is probably mediated through two different mechanisms, since only tricyclic antidepressants cause a reduction after acute treatment. Although some of the side effects of antidepressant treatment may be related to the blockade of histamine receptors, these results do not support the assumption that this effect of antidepressant treatment contributes to their clinical effects.