Long-term modulation of presynaptic 5-HT-output: experimentally induced changes in cortical 5-HT-transporter density, tryptophan hydroxylase content and 5-HT innervation density.

Whereas experimentally induced long-term changes of postsynaptic mechanisms of 5-HT neurotransmission have been studied in great detail, much less is currently known about the effects of certain treatments on the presynaptic components governing the output of 5-HT in individual brain regions. This contribution summarizes the results of a series of experiments on the influence of different physiologic and pharmacologic manipulations on three different parameters of 5-HT presynapses, 5-HT transporter density, tryptophan hydroxylase content, and serotonin level in the rat frontal cortex. The combined measurement of several parameters of 5-HT presynapses allows to differentiate between treatments which exclusively affect the density of 5-HT transporters (long-term food restriction), which exclusively affect the level of tryptophan hydroxylase apoenzyme (imipramine treatment of olfactory bulbectomized rats) or which cause a parallel increase (bulbectomy, chronic administration of tranylcypramine to rats with chemical lesions of their cortical 5-HT innervation) or a parallel decrease (administration of p-chloroamphetamine) of both parameters, indicating treatment-induced changes in the density of 5-HT presynapses in the frontal cortex. Each of these changes may lead to an altered output of serotonergic afferences, and may therefore act to either potentiate or to attenuate the impact of serotonin-mediated effects on the activity of local networks located in a certain brain region.