Postsynaptic serotonergic action

Heym, J. Rasmussen, K. and Jacobs, B.L. Some behavioral effects of hallucinogens are mediated by a postsynaptic serotonergic action ... 

This section is a selective review of behavioral pharmacology studies in animals and humans that are consistent with a postsynaptic serotonergic action of LSD-like hallucinogens. (See also the chapters by Davis et al., Appel and Rosecrans, and Nichols and Glennon, this volume.)... 

Postsynaptic Serotonergic Action of Hallucinogens Barry L. Jacobs... 

We are still confronted by a list of interesting and important questions that have not been answered. To what extent are dopamine pathways involved in hallucinogenic drug action What is the relative importance of presynaptic versus postsynaptic serotonergic action Is the release of endogenous neurotransmitters... 

Fornal, C.R.M. Sleep suppressant action of fenfluramine in rats. I. Relation to postsynaptic serotonergic stimulation. J. Pharmacol. Exp. Ther. 225 667, 1953. 

Jacobs, B. L., Rasmussen, K., and Heym, J. (1982) Evidence that some of the behavioral effects of LSD are mediated by a direct action at postsynaptic serotonergic receptors. Soc. Neurosci. Abstr., 8 390. 

Recently research has focused on the action of lithium on serotonergic function. Lithium has been shown to facilitate the uptake and synthesis of 5-HT, to enhance its release and to increase the transport of tryptophan into the nerve terminal, an effect which probably contributes to the increased 5-HT synthesis. The net effect of these changes is to produce postsynaptic receptor events, which might explain why lithium, in combination with tryptophan and a monoamine oxidase inhibitor or a 5-HT uptake inhibitor, is often effective in therapy-resistant depression. 

Figure 7. A serotonergic synapse including a depiction of the acute tryptophan depletion method discussed in the text. All large neutral amino acids (SLNAAs) share a common blood-brain barrier transporter. The serotonergic precursor, tryptophan, essentially competes with the other LNAAs for transport. Thus tryptophan is uniquely susceptible to acute dietary manipulation. Numerous serotonergic receptor types exist, including presynaptic S-HTm and (somatodendritic) 5-HTia autoreceptors and postsynaptic 5-HTia, 5-HTid, 5-HT2a 5-HT2c 5-HT3 and 5-HT4 receptors. Additional modulation of serotonin activity can occur via the action of selective serotonin re-uptake inhibitors (SSRls) including fluoxetine, fluvoxamine, and citalopram.

Tricyclic antidepressants act both presynaptically and postsynaptically on two major systems, the norader-nergic and the serotonergic. The actions of TCAs in each system will be discussed separately. Figure 23.2 shows an overall schematic of the receptor blockade of TCAs. 

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