Electrophysiological assessment of the effects of antidepressant treatments on the efficacy of 5-HT neurotransmission

Abstract

The efficacy of serotoninergic (5-HT) neurotransmission was assessed in the rat brain following different types of antidepressant treatments. First, the firing rate of 5-HT neurons was assessed. Second, the responsiveness of postsynaptic neurons to 5-HT was evaluated by applying directly onto these neurons the neurotransmitter by microiontophoresis. Finally, the effect of the electrical stimulation of the 5-HT pathway on the firing activity of the same postsynaptic neurons was studied in order to determine the efficacy of synaptic transmission. Long-term administration of tricyclic antidepressant drugs induces a sensitization of rat forebrain neurons to 5-HT without altering 5-HT neuron properties. This sensitization results in an enhancement of the effect of the stimulation of the 5-HT pathway on the firing activity of postsynaptic neurons. Long-term administration of antidepressant monoamine oxidase inhibitors also results in an enhancement of the effectiveness of the stimulation of the 5-HT pathway. This is not due to a modification of postsynaptic neuron properties, since there is no enhancement of their responsiveness to 5-HT. Furthermore, the function of the terminal 5-HT autoreceptor is not altered by long-term treatment with a monoamine oxidase inhibitor. Therefore, the enhancement of 5-HT neurotransmission produced by this type of drugs is due to an increased availability of releasable 5-HT. The acute administration of 5-HT reuptake blockers does not enhance the efficacy of the stimulation of the 5-HT pathway. However, their long-term administration produces such an enhancement without altering the responsiveness of postsynaptic neurons to 5-HT. This modification of 5-HT transmission is attributable to a desensitization of the terminal 5-HT autoreceptor, thereby allowing a greater amount of 5-HT to be released per impulse in the synaptic cleft. The electrophysiological assessment of the effects of these different types of antidepressant treatments on the 5-HT system therefore revealed as a common effect an enhancement of 5-HT neurotransmission, albeit each one achieving this via a different mechanism.