Serotonin neurotransmission

Moore, R.Y. The anatomy of central serotonergic neuron systems in the rat brain. In Jacobs, B.L., and Gelperin, A., eds. Serotonin Neurotransmission and Behavior. Cambridge, MA MIT Press, 1981. pp. 35-71. 

Plants affecting the serotoninergic neurotransmission are therefore interesting because of their potentials for the treatment of depression, which is the eighth leading cause of death in the United States. It is generally agreed that there is a correlation between diminished serotonin neurotransmission and episodes of major depression, and a number or inhibitors of serotonin-uptake inhibitors are available on the market, such as sertraline (Zoloft ). 

Reneman L, Booij J, Schmand B, Brink W, Gunning B (2000). Memory disturbances in Ecstasy users are correlated with an altered brain serotonin neurotransmission. Psychopharmacology, 148, 322-324. 

A number of medications used in the treatment of anxiety have effects on serotonin neurotransmission (Ch. 13). These medications include tricyclic antidepressant medications, SSRIs, and monoamine oxidase inhibitors (MAOIs). However, because these medications take weeks to exert their full anxiolytic effects, it is unlikely that blocking the reuptake (and thus increasing synaptic levels) of either serotonin or norepinephrine selectively is responsible for their anxiolytic properties — rather it is suspected that the therapeutic effects are due to changes in gene expression, protein levels, and eventually changes in synaptic connections between neurons. 

Anderson, E. G., and Proudfit, H. K. (1981) The functional role of the bulbospinal serotonergic nervous system. In Serotonin, Neurotransmission and Behavior, edited by B. L. Jacobs and A. Gelperin, pp. 307-338. MIT Press. Cambridge. 

As discussed above, what is the exact nature of the interaction between hallucinogenic drugs and serotonin neurotransmission Is this effect characteristic... 

Robinson TE, Camp DM. 1991. The effects of four days of continuous striatal microdialysis on indices of dopamine and serotonin neurotransmission in rats. J Neurosci Methods 40(2-3) 211-222. 

There is another reason why medications exert multiple effects. For example, an antidepressant that very specifically promotes serotonin neurotransmission and has little or no interaction with other receptor types will still produce multiple effects. How can this be Remember that in different areas of the brain, a single neurotransmitter can assume very distinct roles. When an individual takes a medication that alters the activity of a particular neurotransmitter, it generally does so throughout the brain. Consequently, the dopamine receptor blocking effect of haloperidol (Haldol) reduces hallucinations and paranoia in one brain region but causes upper extremity stiffness through its action in another brain region. 

Hashimoto S, Inoue T, Koyama T (1999) Effects of conditioned fear stress on serotonin neurotransmission and freezing behavior in rats. Eur J Pharmacol 378 23-30 Hayley S, Borowski T, Merali Z, Anisman H (2001) Central monoamine activity in genetically distinct strains of mice following a psychogenic stressor effects of predator exposure. Brain Res 892 293-300... 

Mecfianism of Action A tetracyclic compound that acts as an antagonist at presynap-tic alphaj-adrenergic receptors, increasing both norepinephrine and serotonin neurotransmission. Flas low anticholinergic activity. Therapeutic Effect Relieves depression and produces sedative effects. 

Murphy, D.L., Andrews, A.M., Wichems, C.H., Li, Q., Tohda, M., and Greenberg, B. (1998) Brain serotonin neurotransmission an overview and update with an emphasis on serotonin subsystem heterogeneity, multiple receptors, interactions with other neurotransmitter systems, and consequent implications for understanding the actions of serotonergic drugs. J Clin Psychiatry 59 5uppl 15 4-12. 

Recent investigations into intracellular events have begun to define the postsynaptic events through which TCAs appear to exert their effects (Morinobu et ah, 1995). One of the observations made was down-regulation of transcription factors for early gene products such as c-Fos. C-Fos is normally produced in response to periods of stress. In research with rats, TCAs as well as other antidepressants have been shown to decrease the expression of c-Fos in areas of frontal cortex after chronic but not acute treatment. Other psychotropic medications (e.g., cocaine and haloperidol) with similar acute effects on norepinephrine/serotonin neurotransmission have not shown this same chronic effect. It has been speculated that the decreased production of c-Fos is the end product of a cascade of events stimulated by increased norepinephrine levels (Morinobu et ah, 1995). 

Thyroid function also seems to be enhanced in people with PTSD. Again, it is not known if this occurs before or after the onset of symptoms. It is known that thyroid hormone enhances the activity of serotonin, which, as we have seen, is the neurotransmitter most critically involved with maintaining a positive mood. It is possible that people who develop PTSD are those with dysregulation of serotonin neurotransmission. 

Overall, azaperones may decrease serotonin neurotransmission through... 

The delay in onset of anxiolytic and antipanic effects of serotonin reuptake inhibitors and related compounds is still an issue of much speculation. It appears paradoxical that serotonin reuptake inhibitors block serotonin uptake immediately, whereas it takes weeks before their therapeutic effects become apparent. Recently, the idea was advanced that the tentative enhanced serotonin neurotransmission caused by short-term administration of serotonin reuptake inhibitors is offset by negative feedback in the raphe nuclei (Artigas 1993 Blier and de Montigny 1994). The increased level of serotonin in the somatodendritic area, resulting from serotonin uptake inhibition, reduces serotonin neuronal firing through activation of the 5-HTj, autoreceptors. Alterations in the feedback regulation upon repeated administration may... 

Adding lithium. Coadministration of lithium is a proven method for enhancing the thymoleptic action of antidepressants in patients with depression (Heninger et al. 1983). Lithium has been hypothesized to potentiate antidepressant-induced increases in serotonin neurotransmission by enhancing presynaptic serotonin release in some brain regions (Blier and de Montigny 1992]. The success of lithium augmentation in depression and the hypothesized role of serotonin in OCD has prompted studies of the anti-OC efficacy of this approach. 

During the past two decades, there has been increasing evidence that serotonin neurotransmission is diminished during an episode of depression. Drugs that modify 5-HT activity by inhibiting its uptake carrier have been the most clinically productive line of inquiry thus far. 

Synergy within the serotoninergic system. Boosting serotonin neurotransmission has proved to be useful not only in treatment-resistant depression, but for treatment resistance within the whole family of serotonin spectrum disorders, such as obsessive-compulsive disorder, panic disorder, social phobia, posttraumatic stress disorder, and bulimia. 

Some antidepressants—specifically, tricyclics like imipramine (trade name Tofranil) and amitryptiline (trade name Elavil)—are thought to exert their antidepressant effect through inhibition of a reuptake mechanism that sucks back the neurotransmitters from the synapse into the neuron for storage and future use, a process mentioned in Chapter 1. The resulting net effect is an increase of these molecules at the synapse and thus a more robust neurotransmission. A different category of antidepressants—monoamine oxidase inhibitors (MAOIs)—display a different mechanism of action but with the same net effect of increasing norepinephrine and serotonin neurotransmission they inhibit the metabolism (breakdown) of the molecules stored in the neurons, thus creating more abundant supplies for neurotransmission. 

Buspirone is an anxiolytic with dopaminergic, noradrenergic and antiserotonergic properties, Anxiolytic properties are attributed to effects on serotonin transmission (probably inhibiting transmission via 5-HTLA autoregulation). It may have postsynaptic 5-HTIA agonist activity and thus facilitate serotonin neurotransmission. 

Blocks alpha 2 adrenergic presynaptic receptor on serotonin neurons (heteroreceptors), thereby increasing serotonin neurotransmission... 

MDMA induces norepinephrine release from presy-naptic vesicles. MDMA also effects serotonin neurotransmission by causing release of serotonin... 

SAD and bulimia nervosa are often co-morbid, and both independently can show a seasonal pattern (Ghadirian et al. 1999). Also, they both respond favourably to SSRI antidepressant drugs. It may be that both disorders reflect similar alterations in central serotonin neurotransmission (Sil-verstone 1993). 

In later life PWS is frequently associated with compulsive behaviour such as skin picking, hoarding, concerns with symmetry, ordering and arranging (Dykens and Shah 2003). Such behaviour might reflect an underlying disturbance in central serotonin neurotransmission as patients are responsive to treatment with serotonin reuptake inhibitors (Dimitropoulos et al. 2000). 

When compared with the selective serotonin reuptake inhibitors (SSRIs), mirtazapine may show an earlier onset of action (although data are currently not well established). Mirtazapine has also been found to be efficacious in the treatment of elderly patients with depression. Mirtazapine has been shown to be effective in the treatment of panic disorder, social phobia, and post-traumatic stress disorder. In one study, mirtazapine combined with citalopram in obsessive-compulsive patients induced an earlier response when compared with citalopram plus placebo. It was suggested that antagonism of presynaptic a2-adrenergic receptors does not enhance serotonin neurotransmission directly, but rather disinhibits the norepinephrine activation of serotonergic neurons and thereby increases serotonergic neurotransmission by a mechanism that may not require a time-dependent desensitization of receptors. 

A leading hypothesis suggests that depression is caused by impaired monoamine (e.g., norepinephrine, dopamine, serotonin) neurotransmission. Drugs which induce monoamine release are indicated for attention deficit disorder and narcolepsy. The biochemical disturbance responsible for these two diseases is unknown. 

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