Synapse serotonergic

Berger, U. Hung, G. Molliver, M.E. and Grzanna, R. Psychotropic amphetamines have different sites of action at serotonergic (5-HT) synapses A eomparison of p-chloroamphetamine (PCA) and 3,4-methyl-enedioxyamphetamine (MDA) with 2,5-dimethoxy-4-methylamphetamine (DOM). Abstr Soc Neurosci 13 906, 1987. 

Hensler, J. G., Ferry, R. C., Labow, D. M., Kovachich, G. B. 8r Frazer, A. (1994). Quantitative autoradiography of the serotonin transporter to assess the distribution of serotonergic projections from the dorsal raphe nucleus. Synapse 17, 115. 

Schizophrenia is a chronic, complex psychiatric disorder affecting approximately 1% of the population worldwide. The chronic nature of the illness, in addition to the early age of onset, results in direct and indirect health care expenditures in the U.S., which amount to approximately 30 to 64 billion dollars per year [4]. It is perhaps the most devastating of psychiatric disorders, with approximately 10% of patients committing suicide. The dopamine hypothesis of schizophrenia postulates that overactivity at dopaminergic synapses in the central nervous system (CNS), particularly the mesolimbic system, causes the psychotic symptoms (hallucinations and delusions) of schizophrenia. Roth and Meltzer [5] have provided a review of the literature and have concluded a role for serotonin as well in the pathophysiology and treatment of schizophrenia. The basic premise of their work stems from the known interaction between the serotonergic and dopaminergic systems. 

The activity of 5-HT in the synapse is terminated primarily by its re-uptake into serotonergic terminals 234 Acute and chronic regulation of serotonin transporter function provides means for altering synaptic 5-HT concentrations and neurotransmission 236... 

The activity of 5-HT in the synapse is terminated primarily by its re-uptake into serotonergic terminals. 

In conclusion, in vitro as well as in vivo studies with 3H-LSD revefiled that specific sites which bind the labeled hallucinogen do exist in brain. These sites apparently do not correspond to receptors for hallucinogens but to specific postsynaptic receptors for 5-HT. It can be inferred that serotonergic synapses may be a preferential target for hallucinogens, at least for those of the LSD series. As discussed below, numerous biochemical investigations on brain 5-HT metabolism confirm this hypothesis. 

Jacobs, B. L. (1976) An animal behavior model for studying central serotonergic synapses. Life Sci., 19 777-786. 

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.

Dluzen DE, Anderson LI, McDermott JL, Kucera J, Walro JM (2002) Striatal dopamine output is compromised within +/- BDNF mice. Synapse 43 112-117 Donovan SL, Mamounas LA, Andrews AM, Blue ME, McCasland JS (2002) GAP-43 is critical for normal development of the serotonergic innervation in forehrain. J Neurosci 22 3543-3552... 

While much emphasis has been placed on alterations in noradrenergic neurotransmission, TCA drugs are not without effect on serotonin (5-HT) neurotransmission. Long-term studies with TCA drugs in animals have demonstrated postsynaptic supersensitivity to serotonin (5-HTia) receptor agonists at serotonin synapses, with an associated enhancement of serotonergic neurotransmission. The sensitization to 5-HTia agonists is mediated in part by an increase in the density of postsynaptic 5-HTia receptors. Enhancement of trans-... 

FIGURE 2.6 Serotonergic synapse. Serotonin binds to at least seven different receptors. The most relevant are the 5-HTi receptors (1), 5-HT2 receptors (2), and 5-HT3 receptors (3). Antagonists of the 5-HT2 receptor include nefazodone and the majority of atypical antipsychotic drugs. The serotonin transporter (4) pumps serotonin back into the serotonergic neuron, which can be blocked by drugs such as venlafaxine, clomipramine, imipramine, and amitriptyline. 

Kosofsky BE, Molhver ME The serotonergic innervation of cerebral cortex different classes of axon terminals arise from dorsal and median raphe nuclei. Synapse 1 153-168, 1987... 

Reuptake through the presynaptic membrane is the major deactivation mechanism for serotonin. It is prevented by the tricyclic antidepressants (see section 4.3.7), among which the tertiary amines are more potent at serotonergic terminals than are the secondary bases, whereas the reverse is true for catecholaminergic synapses. 

Another important mechanism whereby the release of a neurotransmitter may be altered is by presynaptic inhibition. Initially this mechanism was thought to be restricted to noradrenergic synapses, but it is now known to occur at GABA-ergic, dopaminergic and serotonergic terminals also. 

Tamir H, Hsiung SC, Yu PY, et al. Serotonergic signalling between thyroid cells protein kinase C and 5-HT2 receptors in the secretion and action of serotonin. Synapse 1992 12 155-168. 

Sprouse JS, Aghajanian GK. Electrophysiological responses of serotonergic dorsal raphe neurons to 5-HT1A and 5-HT1B agonists. Synapse 1987 1 3-9. 

MAOIs increase the concentrations of NE, 5-HT, and DA within the neuronal synapse through inhibition of the MAO enzyme. Studies have demonstrated that similarly to TCAs, chronic therapy causes changes in receptor sensitivity (i.e., downregulation of 8-adrenergic, a-adrenergic, and serotonergic receptors)." " The MAOIs currently marketed in the U.S., phenelzine and tranylcypromine, are nonselec-tive inhibitors of MAO A and MAO B. 

---