The electrophysiologic assessment of the action of different types of antidepressant treatments on the serotonin (5-hydroxytryptamine [5-HT]) system revealed as a common effect an enhancement of 5-HT neurotransmission, albeit each treatment achieved this result via a different mechanism. Tricyclic antidepressant drugs and electroconvulsive shock treatment sensitize postsynaptic neurons to 5-HT. Monoamine oxidase inhibitors enhance the availability of releasable 5-HT. Serotonin reuptake blockers increase the efficacy of 5-HT neurons by desensitizing 5-HT autoreceptors located on 5-HT nerve terminals. Serotonin1A receptor agonists would enhance the tonic activation of postsynaptic 5-HT1A receptors. Such results suggest that this effect of antidepressant treatments on the 5-HT system might be intimately related to their therapeutic effect in major depression.