Species dependence of adaptations at the pre- and postsynaptic serotonergic receptors following long-term antidepressant drug treatment.

Rats were treated daily for 3 weeks with the antidepressant amitriptyline, and adaptations following this treatment at the level of the postsynaptic 5-HT2 receptor were studied, as well as the presynaptic serotonin re-uptake and the 5-HT autoreceptor functioning. Rabbits were treated chronically with one of the antidepressants amitriptyline, imipramine, chlorimipramine and mianserin, and the occurrence of the different pre- and postsynaptic adaptations were compared to what was observed in rat brain. Postsynaptic 5-HT2 receptors were down-regulated following a long-term antidepressant drug treatment in rat prefrontal cortex, but were unchanged in rabbit brain. Two markers for presynaptic 5-HT uptake were used to evaluate differences between control and treated animals: in rat brain a decreased number of [3H]imipramine binding sites was observed, however, without any change in the kinetics of the [3H]5-HT accumulation. In rabbit brain, both [3H]imipramine binding and [3H]5-HT accumulation remained unchanged. The function of the presynaptic serotonergic autoreceptor was affected, although differentially, in both rat and rabbit brain, following the long-term antidepressant drug treatment. In rat brain, these autoreceptors were down-regulated, whereas in rabbit brain, the results indicated that the autoreceptors were only no longer activated by endogenously released serotonin. The authors hypothesize that the different presynaptic adaptations at the level of the 5-HT autoreceptor are responsible for the absence or presence of a postsynaptic 5-HT2 receptor down-regulation in rat and rabbit brain following a long-term antidepressant treatment.