Serotonin in brain

Haigler, H. J., and Aghajanian, G. K. (1974) Peripheral serotonin antagonists Failure to antagonize serotonin in brain areas receiving a prominent serotonergic input. J Neural Transm., 35 257-274. 

Figure 3.1 This picture shows the presence of serotonin in brain neuron fibers. On the ieft is a normai, untreated brain. The middie picture shows a simiiar area of brain tissue, two weeks after Ecstasy treatment. Notice the dramatic ioss of serotonin staining. The picture on the right was from a monkey treated seven years earlier with Ecstasy. Serotonin staining is still reduced in these brain sections. 

V. Petkov et al. G115 extract increases dopamine and serotonine in brain stem of... 

Matos FF, Rollema H, Basbaum AI (1992) Simultaneous measurement of extracellular morphine and serotonin in brain tissue and CSF by microdialysis in awake rats. J Neurochem 58 1773-1781. 

Luo et al. [43] described an electrode based on the incorporation of CNTs for the simultaneous determination of dopamine, ascorbic acid and serotonin. By using differential pulse voltammetry, dopamine could be deteeted in the range of 0.5 to 10 pM in the presence of 5 pM serotonin and 0.5 mM aseorbie aeid, with a detection limit of 0.1 pM. For serotonin, the signal was linear between 1.0 and 15 pM in the presence of 5 pM dopamine and 0.5 mM aseorbie aeid, with a detection limit of 0.2 pM. No interference was reported on the determination of 5 pM dopamine and 5 pM 5-hydroxytiyptamine in the presenee of 10-fold excess dopae, 5-fold excess uric acid, 200-fold excess oxalate and 500-fold exeess glueose. Excellent reproducibility was also reported. No interferenee was observed in the determination of dopamine and serotonin in brain of rabbit. 

Baron SA, Testa FM, Gintzler AR (1985) Simultaneous quantitation of norepinephrine, dopamine and serotonin in brain during and following chronic naltrexone administration. Brain Res 340 192-198... 

Kuhar M. J., Shaskan, E. G. and Snyder, S. H. (1971) The subcellular distribution of endogenous and exogenous serotonin in brain tissue comparison of synaptosomes storing serotonin, norepinephrine and y-aminobutyric acid. J. Neurochem., 18 333-343. 

Reserpine (e.g., Sandril) Depletes catecholamines and serotonin in brain, adrenal, and heart. Inhibits uptake of norepinephrine into presynaptic vesicles. Chronically sensitizes patient to sympathomimetics. Gradual 4 mean arterial pressure with bradycardia. Antihypertensive effects due to 4 cardiac output. Tranquilization, sedation. Nightmares, depression, diarrhea, cramps, T risk of breast cancer, peptic ulcers, parasympathetic predominance. 

Ponzio, F., and Jonsson, G., 1979, A rapid and simple method for the determination of picogram levels of serotonin in brain tissue using liquid chromatography with electrochemical detection,/. Neurochem. 32 129-132. 

Sasa, S., and Blank, C. L., 1979, Simultaneous determination of norepinephrine, dopamine, and serotonin in brain tissue by high-pressure liquid chromatography with electrochemical detection. Anal. Chim. Acta 104 29-45. 

Southern, A. L. and Christoff, N., Cerebrospinal fiuid serotonin in brain tumor and other neurological disorders determined by a spectrophotofluorimetric technique, /. Lab. Clin. Med. 59, 320 (1962). 

The neurokinin, substance P (SP), may be involved as a sensory transmitter in afferent vagal nerves involved in the vomiting reflex. Both SP and its receptors (NKi receptors) have been detected in several areas of the brain associated with vomiting, including the AP, NTS and dorsal motor vagal nucleus. The neurokinin can activate neurons in the AP and NTS. SP is present also in sensory nerves in the gut as well as being co-localised with serotonin in some enterochromaffin cells. 

An additional study reported age-dependent effects. Lakshmana and Raju (1994) found that oral treatment of rat pups with endosulfan from postnatal days 2-10 resulted in changes in the concentration of noradrenalin, dopamine, and serotonin in various brain areas that differed either in magnitude or direction from changes seen in pups treated from postnatal days 2-23. While the results from this study do not necessarily indicate that neonates are more sensitive to the toxic effects of endosulfan, they do show that the duration of exposure in neonates is an important parameter to consider. 

Lakshmana MK, Raju TR. 1994. Endosulfan induces small but significant changes in the levels of noradrenaline, dopamine and serotonin in the developing rat brain and deficits in the operant learning performance. Toxicology 91(2) 139-50. 

Takahashi, H, Takada, Y, Nagai, N, Urano, T and Takada, A (1998) Extracellular serotonin in the striatum is increased after immobilisation stress only in the nighttime. Behav. Brain Res. 91 185-201. 

Ferrer, A and Artigas, F (1994) Effects of single and chronic treatment with tranylcypromine on extracellular serotonin in rat brain. Eur. J. Pharmacol. 263 227-234. 

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. 

COMMENT We feel that it is due to the formation of 5,6-DHT in the eortex. These cells are indeed innervated by serotonin cells and, as a matter of fact, we have an experiment that is being published in Brain Research where we show that if we injeet 5,6-DHT into the ventricles, we ean produce exactly the same type of degeneration in the pyramidal cells, due to the formation of the 5,6 from the 5-hydroxytryptamine. We are exploring the possibility of it being another catecholamine in addition to dopamine, so I think both of those may be helpful in answering your question. 

Steranka, L. Bessent, R. and Sanders-Bush, E. Reversible and irreversible effects of -chloroamphetamine on brain serotonin in mice. Comm Psychopharmacol 1 447-454, 1977. 

Typically, neurotoxic effects of drugs on monoamine neurons have been assessed from reductions in brain levels of monoamines and their metabolites, decreases in the maximal activity of synthetic enzymes activity, and decreases in the active uptake carrier. In the present study, the traditional markers described above have been used, including the measurement of the content of monoamines and their metabolites in brain at several different timepoints following drug administration. Since reports in the literature have documented that MDMA and MDA can inhibit the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin synthesis (Stone et al. 1986 Stone et al. 1987). it is unclear whether MDMA-induced reductions in the content of serotonin and its metabolite 5-hydroxyin-doleacetic acid (5-HlAA) may be due to suppressed neurotransmission in otherwise structurally intact serotonin neurons or may represent the eonsequenee of the destruction of serotonin neurons and terminals. 

It was of interest that, in spite of the recovery of serotonin uptake sites to control levels, the content of serotonin in the same brain region remained markedly (40 to 50 percent) below age-matched controls for as long as 1 year after MDMA administration. It is unclear from these data whether there is a regeneration of axons that have previously undergone degeneration or whether the increased density of uptake sites is a consequence of increased collateral sprouting of neurons unaffected by the drug treatment. 

The data presented in this chapter provide strong evidence, from both neurochemical and neuroanatomical studies, demonstrating that, following in vivo administration of a number of methylenedioxy-substituted amphetamine derivatives, there is widespread and long-lasting degeneration of serotonin neurons in brain, without any major or consistent effects on catecholamine neurons. A detailed examination of the parameters involved in the neurotoxic and neurodegencrative effects of MDMA on brain serotonin neurons indicates that ... 

As shown in table 6, we have compared the affinities of a series of methylenedioxy derivatives with those of the parent compounds (amphetamine and methamphetamine) at some of the recognition sites in brain at which MDMA exhibited the highest affinities. These comparative studies indicate that addition of the methylenedioxy subshtuent in the 3,4 position inereases their affinity at serotonin uptake, 5-HT2 serotonin, and M-1 muscarinic receptors, while the unsubstituted parent compounds appear to be more potent at Ct2-iadrenergic receptors. 

Aghajanian, G.K. and Vandermaelen, C.P. Specific systems of the reticular core Serotonin. In Mountcastle, V.B. Bloom, F.E. and Geiger, S.R., eds. Handbook of Physiology, Volume IV. Intrinsic Regulatory Systems of the Brain. Bethesda, MD American Physiological Society, 1986. pp. 237-256. 

Bogdanski, D.F. Weissbach, H. and Udenfriend, S. The distribution of serotonin, 5-hydroxytryptophan decarboxylase, and monoamine oxidase in brain. J Neurochem 1 272-278, 1957. 

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