Acute regulation and long-term modulation of presynaptic serotonin output

This contribution summarizes the present knowledge about the mechanisms involved in the regulation of presynaptic serotonin release. Under conditions of a permanently altered environmental, (psychosocial, drug-induced, nutritional etc.) input, each one of these mechanisms may be adaptively adjusted to the novel use-dependent requirements. Examples of such long-term alterations of the 5-HT-output pattern in distant projection fields of the raphe-neurons are the downregulation of cortical serotonin-transporters after long-term food restriction, the loss of serotonergic nerve terminals caused by substituted amphetamines, the serotonergic hyperinnervation of the frontal cortex seen after olfactory bulbectomy in rats, or the long lasting changes in the levels of tryptophanhydroxylase, of serotonin-transporter depression or in the density of serotonergic nerve terminals in distant projection fields caused by long-term antidepressant treatments. All these long-lasting alterations and imbalances of a previously established serotonin-output-pattern will not only affect the impact of individual regional networks on whole brain information processing but also the established synaptic connectivity in distant projection fields of the central serotonergic system.