Serotonin pathways

In view of the apparent pleasurable effects of MDMA, it becomes of considerable interest to understand the mechanism of action of substances with a similar effect. Major efforts have been directed toward the study of agents that have an effect on serotonin pathways, since that is the neurotransmitter system that seems most implicated in the mechanism of action of MDMA. This hypothesis is further reinforced by the observation that MDMA substitutes for fenfluramine (Schechter 1986). and fenfluramine substitutes for MBDB (Oberlender and Nichols, unpublished). The substitution data for (+)-amphetamine and cocaine in (-t-)-MBDB-trained rats are also similar to the data for substitution of these agents in fenfluramine-trained rats (White and Appel 1981). 

Stone, D.M. Merchant, K.M. Hanson, G.R. and Gibb, J.W. Immediate and long-term effects of 3,4-methylenedioxymethamphetamine on serotonin pathways in brain of rat. Neuropharmacology 26 1677-1683, 1987b. 

Serretti, A., Benedetti, F., Zanardi, R. Smeraldi, E. (2005). The influence of serotonin transporter promoter polymorphism (SERTPR) and other polymorphisms of the serotonin pathway on the efficacy of antidepressant treatments. Prog. Neuro psychopharmacol. Biol. Psychiatry, 29(6), 1074-84. 

Tramadol is an opioid analgesic, which acts by exerting an opioid effect and through the stimulation of adrenergic and serotonin pathways. Compared with the other opioids, tramadol is less likely to cause the typical opioid side-effects, such as respiratory depression, and constipation. It is also less likely to cause addiction. 

Serotonin (5-hydroxytryptamine [5-HT]) pathways play an important role in postprandial satiety. Treatments that increase intrasynaptic serotonin or directly activate serotonin receptors tend to reduce food consumption, whereas interventions that dampen serotonergic neurotransmission or block receptor activation reportedly increase food consumption and promote weight gain (Blundell, 1984 Teibowitz, 1986). Moreover, CNS serotonin pathways have been implicated in the modulation of mood, impulse regulation and be-... 

Most 5-hydroxytryptamine (5-HT, serotonin) pathways originate from neurons in the raphe or midline regions of the pons and upper brain stem. 5-HT is contained in unmyelinated fibers that diffusely innervate most regions of the CNS, but the density of the innervation varies. 5-HT acts on more than a dozen receptor subtypes. Except for the 5-HT3 receptor, all of these... 

C. Serotonin pathways and receptors that mediate therapeutic actions and side effects of SSRIs... 

Once the 5HT1A somatodendritic autoreceptors are desensitized, 5HT can no longer effectively inhibit its own release, and the serotonin neuron is therefore dis-inhibited. This results in a flurry of >HT release from axons due to an increase in neuronal impulse flow (Fig. 6—38). This is just another way of saying that the serotonin release is turned on at the axon terminals. The serotonin that now pours out of the various projections of serotonin pathways in the brain theoretically mediates the various therapeutic actions of the SSRls. 

Serotonin Pathways and Receptors That Mediate Therapeutic Actions and Side Effects of SSRIs... 

As mentioned above, the SSRIs cause both their therapeutic actions and their side effects by increasing serotonin at synapses, where reuptake is blocked and serotonin release is disinhibited. In general, increasing serotonin in desirable pathways and at targeted receptor subtypes leads to the well-known therapeutic actions of these drugs. However, since SSRIs increase serotonin in virtually every serotonin pathway... 

Serotonin pathways are involved in the regulation of prolactin secretion. Amenorrhea, galactorrhea, and hyperprolactinemia have been reported in a patient taking SSRIs. 

Vaginal bleeding and menorrhagia have been rarely reported with SSRI treatment and the mechanism is uncertain. SSRIs have been associated with bleeding diatheses, which might explain these observations (SEDA-24, 15) (SEDA-25,14). Another possibility is an action of serotonin pathways on the neural regulation of gonadotropin release. More cases have been reported. 

Drugs that potentiate the function of serotonin, such as venlafaxine, can produce pharmacodynamic interactions with dopamine receptor antagonists, perhaps because serotonin pathways can inhibit dopamine neurotransmission. 

Finally, it was found (B7) that the excretion of 5-hydroxyindoleacetic acid, which is taken as an index of tryptophan metabolism by the serotonin pathway, is affected by the administration of tryptophan neither in normal nor in schizophrenic subjects. 

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