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- <p><strong>Serotonin: Effects in disease, aging and inflammation</strong></p>
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- Interpreting medical publications requires some skills that aren't needed for understanding more strictly
- scientific reports, because medical writing often takes into account the fact that physicians spend most of
- their time interacting with the public, rather than studying. The public's understanding of medicine is
- shaped by "public relations," by the introduction of words and concepts that frame the argument. (The
- linguist George Lakoff summarized the essence of public relations by observing that people reject facts that
- are outside their view of reality, their mental framework.) Television and public schools now frame the
- worldview of the affluent cultures, according to the needs of the ruling powers. Long before specific
- prescription drugs could be advertised directly to consumers, the medical and pharmaceutical industries were
- creating a favorable frame for their products.Many years ago, public relations experts used expensive
- opinion polls to judge the effectiveness of their efforts, but now there is a convenient way to see how the
- general public is thinking: Wikipedia, the internet encyclopedia. The success of corporate advertising can
- be seen in their recent article on serotonin, which says "It is a well-known contributor to feelings of
- well-being; therefore it is also known as a 'happiness hormone' despite not being a hormone."The culture
- that has happy and unhappy hormones was a culture in which each hormone had a receptor, a substance in a
- cell which, when its ligand was bound to it, made the cell do something. Although that culture still has
- influence in the 21st century, discoveries made between 1940 and 1970 showed that those mechanical ideas of
- receptors didn't reflect biological reality. Albert Szent-Gyorgi and the Pullmans showed that the electronic
- qualities of molecules determined their functions, and Szent-Gyorgyi showed that the state of the cell,
- tissue, and organism governed the effect of hormones and drugs. In the 1960s, substances with very different
- biological effects, such as acetylcholine and adrenaline, were shown to be selectively bound to the same
- cellular site in some cells. It was primarily the drug industry that created and sustained the specific
- receptor doctrine. That doctrine suited the recognition of their public relations- marketing experts, that
- successful advertising had to be directed at the sixth-grade educational level. The ideas of bioelectronics
- and context-sensitive molecules, like morphogenetic fields, were just too complicated to sell well.Although
- metaphorical thinking can be creative and productive, metaphors mustn't be taken literally. The
- identification of multiple types of receptor for a given natural substance involves the use of different
- substances as metaphors or similes for the natural substance. That type of pharmacology is slowly being
- replaced by an attempt to understand state-dependent sensitivities. The energetic state of a cell, and of
- the whole organism, determines the meaning of events and conditions, such as the presence of the "regulatory
- substances."The receptor culture can be tentatively disregarded when thinking about the history of
- serotonin. In the 1930s Vittorio Erspamer identified an amine in the intestine, that caused the intestine to
- contract. Then a group in England extracted an amine from serum that caused blood vessels to contract, and
- identified its chemical nature. Later, Erspamer showed that the intestinal amine and the vascular amine were
- chemically the same. The English group who had identified the substance by extracting tons of beef blood,
- wanted to find sensitive ways to assay it for further studies, and in 1951 they gave a sample to a
- pharmacologist, John Gaddum, who tested its effects on tissues including blood vessels and rat
- uteruses.Gaddum tested the serotonin in combination with a variety of other drugs, including ergot
- derivatives, that he knew acted on smooth muscles, and very soon observed that LSD blocked the effects of
- serotonin. Since he knew that LSD produced mental effects (Sandoz had distributed samples of it to
- researchers in 1947), he reasoned that the brain might also contain serotonin, and by 1952 was able to
- demonstrate that it does contain small amounts of it. A couple of years later he suggested "that the mental
- effects of lysergic acid diethylamide are due to interference with the normal action of this HT [5-
- hydroxytryptamine, serotonin]." At the Rockefeller Institute in New York, Woolley and Shaw also saw the
- antagonistic effects on smooth muscle, and drew similar conclusions about the brain. Erspamer (Renic. sc.
- farmital. 1, 1, 1954) showed that LSD was a highly effective antagonist against the antidiuresis caused by
- serotonin (enteramine).Around the same time, in the early 1950s, several people recognized that the symptoms
- produced by administering an excess of serotonin were similar to those experienced by people with intestinal
- tumors called argentaffinomas or carcinoid tumors, which are usually in the small intestine or appendix. The
- normal intestine contains about 95% of the serotonin in the body (and the brain normally contains only about
- 1%), and in the normal person only about 1% of the dietary tryptophan is converted to serotonin. But in an
- advanced case of carcinoid, 60% of the tryptophan can be turned into serotonin. Especially if the tumor has
- invaded the liver, the serotonin won't be destroyed by the liver in the usual way, and will circulate in the
- bloodstream at high levels, producing symptoms of flushing, sweating (sometimes dark-colored), diarrhea
- (serotonin stimulates small intestine smooth muscle, but inhibits the large [Bennett & Whitney, 1966]),
- nausea, anxiety, reduced urination, muscle and joint pains, and, in late stages, very often cardiovascular
- disease (especially inflammation, fibroma and calcification of the valves in the right side of the heart)
- and aggressive behavior (Russo, et al., 2004) and psychosis.Testing Gaddum's idea of antagonism between LSD
- and serotonin in humans, Montanari and Tonini found that intramuscular injections of serotonin antagonized
- the psychological effects of LSD. Other drugs, especially other ergot derivatives, were more successful than
- LSD in blocking the effects of serotonin (Dubach and Gsell, 1962). There have been suggestions that
- pregnancy hormones could control serotonin excess (McCullough and Myers, 1965). Since estrogen promotes
- serotonin, progesterone is likely to be the protective factor (Donner & Handa, 2009; Hiroi, et al.,
- 2006; Berman, et al., 2006; Bethea, et al., 2000).More recently (Spigset, et al., 2004), it was found that
- LSD binding to a presumed serotonin receptor was low in carcinoid patients, supporting the idea of
- antagonism between the substances, but in the older studies symptoms, rather than competition for binding to
- certain proteins, were the focus of attention. The effects produced by injections and oral doses of
- synthetic serotonin, and of substances that block the synthesis of serotonin, were studied in both animals
- and humans. When a symptom such as clotting, flushing, or diarrhea is produced by serotonin itself, or
- prevented by a blocker of serotonin synthesis, "receptors" aren't an issue.Aldous Huxley was one of the
- first people to think about the general biological meaning of drugs such as LSD. Referring to the ideas of
- Henri Bergson and William Blake, he suggested that the brain usually acts as a filter, or "reducing valve,"
- to make us disregard most of the information we are receiving through our senses, and that the psychedelic
- drugs temporarily remove the filter, or open the sensory reducing valve. Bergson had suggested that the
- filter was a practical measure needed to allow us to focus on practical survival needs; Blake had suggested
- that the doors of perception were kept closed for cultural reasons.Some recent reviews have discussed the
- evidence supporting the serotonin system as primarily inhibitory and protective (Anne Frederickson, 1998,
- Neil Goodman, 2002). Goodman describes the serotonergic system as one of our "diffuse neuroregulatory
- systems," and suggests that drugs such as LSD weaken its inhibitory, filtering effect. (Jacobs, 1983, 1987:
- by changes in the effects of serotonin in the brain, produced by things that affect its synthesis, release,
- catabolism, or receptor action.) LSD depresses the rate of firing of serotonergic nerves in the raphe nuclei
- (Trulson and Jacobs, 1979) causing arousal similar to stimulation of the reticular formation, as if by
- facilitating sensory input into the reticular formation (Bowman and Rand, 1980).In European culture, some
- people--e.g., Plato, Descarte, Locke, Eccles, probably even B.F. Skinner--have believed that mind and body
- are essentially different things (analogous to computer hardware and its programs), while another
- tradition--Blake, Lamarck, Darwin, C.L. Morgan, Pavlov, Reich, C.R. Cloninger, for example--has emphasized
- the continuity of consciousness and character with the body.Understanding the authoritarian personality has
- been an important issue in the 20th century. Wilhelm Reich used some old ideas about the nervous system that
- were current near the beginning of the century, and Cloninger (1995) and others (Netter, et al., 1996,
- Ruegg, et al., 1997, Gerra, 2000), toward the end of the century, were able to incorporate the newer
- information about the serotonergic-dopaminergic antagonisms. In this newer view, high serotonin production
- causes behavioral inhibition and harm avoidance, which are traits of the authoritarian personality, while
- anti-authorians tend to have "novelty seeking" personalities, with high dopamine and low serotonin
- functions.In the 1960s, experimenters put electrodes into a chicken's optic nerve, and when the chicken saw
- a checkerboard pattern, they could measure a patterned electrical activity in the nerve. Without the light
- stimulating the retina, the nerve was quiet. But when they gave the chicken LSD or similar chemicals, they
- recorded patterned electrical activity in the nerve, in the absence of external stimulation. Around the same
- time, other experimenters showed that retinal fatigue quickly desensitized the retina, preventing the
- transmission of impulses to the brain, except when the light pattern corresponded to something familiar,
- showing that impulses from the brain are always involved in renewing, in patterned ways, the sensitivity of
- the retina.The latter experiment shows that everyone's perception involves an outward-directed activity of
- the brain, and the experiments using the chemical stimulants suggested that the intensity of the outward-
- directed action can vary.The inhibitory serotonergic "harm avoidance" system, and the opposing excitatory
- activating "novelty seeking" systems are constantly being influenced by many factors, including nutrition,
- hormones, environmental challenges and opportunities, social interactions, seasons, and the rhythm of night
- and day alternation.Several kinds of research are now showing that the effects of the environment on the
- serotonergic system and its antagonists can influence every aspect of health, not just the personality.For
- example, there have been suggestions that early life isolation of an animal can affect its serotonergic
- activity and increase its anxiety, aggression, or susceptibility to stress (Malick and Barnett, 1976,
- Malick, 1979, dos Santos, et al, 2010), and these effects are associated with increased risk of becoming
- depressed, and developing organic problems. Animals kept in darkness (or with blurring lenses) become
- nearsighted, as the eyeball grows longer under the influence of increased serotonin, and the eyes are
- protected against myopia by serotonin antagonists (George, et al., 2005). The incidence of myopia is
- increasing, at least in countries with industrialized economies, and is more common in females.Migraine
- headaches are also increasing in incidence. By the end of the 1950s, it was widely accepted that migraine
- headaches and associated symptoms including nausea and visual disturbances were caused by an excess of
- serotonin, and antiserotonin drugs of various types were being used for treatment. In one of the early
- studies of the use of LSD in psychotherapy, some of the patients noticed that their chronic headaches had
- stopped. Cluster headaches have also responded well to LSD and similar drugs (Sewell, et al., 2006).Women
- have migraines more often than men do, and they tend to occur in association with ovulation or menstruation.
- Estrogen inhibits monoamino oxidase, MAO, especially the A form that is most active in detoxifying
- serotonin, and it increases the enzymes that control the rate of serotonin synthesis. During serotonin
- excess, the veins and capillaries of the pia mater are engorged with blood, while circulation to the brain
- generally is depressed. Visual symptoms are probably produced by contriction of arterioles, while the pain
- is associated with engorged veins. Progesterone activates the MAO-A, and has other antiserotonin effects on
- blood vessels and nerves.Recently (Shansky, et al., 2010; Figueiredo, et al., 2007), females have been found
- to be more susceptible to stress, and to have reduced uptake of serotonin (prolonging its effects), which
- increases glucocorticoids and ACTH. Kendler, et al. (2005) have found that people with reduced serotonin
- uptake are more susceptible to stress-induced depression.The increase of inhibitory serotonin with stress
- and depression is probably biologically related to the role of serotonin in hibernation, which is an extreme
- example of "harm avoidance" by withdrawal. A diet high in polyunsaturated fat increases the tendency to go
- into hibernation, probably by increasing the brain's uptake of tryptophan. When this is combined with an
- increasingly cold environment, the form of MAO that removes serotonin decreases its activity, while the form
- that removes norepinephrine increases its activity. The metabolite of serotonin, 5-HIAA, decreases, as the
- effect of serotonin increases.In experiments to investigate the mechanism of hibernation, animals were
- injected with serotonin, at different environmental temperatures. In a cool environment, the serotonin
- caused their temperature to fall, by decreasing their heat production, and increasing their loss of heat (by
- causing vasodilation in the skin, "flushing"). In a hot environment, serotonin can cause the animal's
- temperature to rise.Serotonin can reduce the production of energy by inhibiting mitochondrial respiratory
- enzymes (Medvedev, 1990, 1991), and by reduction of oxygen delivery to tissues by vasoconstriction. It also
- appears to interfere with the use of glucose (de Leiva, et al., 1978, Moore, et al., 2004).The brains of
- people with Alzheimer's disease have a decreased ability to metabolize glucose, and high cortisol
- contributes to the altered glucose metabolism, and to the destruction of nerve cells. People with
- Cloninger's "harm avoidance" personality trait, which is closely associated with serotonin (Hansenne, et
- al., 1999), are more likely to develop dementia (Clément, et al., 2010). These observations are consistent
- with the stress-susceptibility of people with high serotonin exposure, and to the effects of cortisol on
- nerves and glucose-derived energy production.Researchers in Brasil have suggested that the serotonergic
- system facilitates conditioned fear, while inhibiting the fight or flight reaction, and that this can
- protectively limit the stress response (Graeff, et al., 1996). "5HT systems reduce the impact of impending
- or actual aversive events. Anticipation of an aversive event is associated with anxiety and this motivates
- avoidance behaviour" (Deakin, 1990). In a stressful situation, the serotonergic nerves can prevent ulcers.
- In other contexts, though, increased serotonin can cause ulcers.The protective, defensive reactions
- involving serotonin's blocking of certain types of reaction to ordinary stresses, are similar to the effects
- of serotonin in hibernation and in Alzheimer's disease (Mamelak, 1997; Heininger, 2000; Perry, et al.,
- 2002). In those extreme conditions, serotonin reduces energy expenditure, eliminating all brain functions
- except those needed for simple survival. These parallels suggest that improving energy production, for
- example by providing ketones as an alternative energy source, while reducing the stress hormones, might be
- able to replace the defensive reactions with restorative adaptive nerve processes, preventing or reversing
- Alzheimer's disease.One of the factors promoting excess cortisol production is intestinal irritation,
- causing absorption of endotoxin and serotonin. Fermentable fibers (including pectins and
- fructooligosaccharides) support the formation of bacterial toxins, and can cause animals to become anxious
- and aggressive. Fed to horses, some types of fiber increase the amount of serotonin circulating in the
- blood. Grains, beans, and other seeds contain fermentable fibers that can promote intestinal irritation.The
- liver has several ways to detoxify endotoxin and serotonin, but these can fail as a result of poor nutrition
- and hypothyroidism.The lung can bind and destroy any excess serotonin that reaches it. A lack of carbon
- dioxide makes platelets release their stored serotonin, and it probably has the same effect in the lung
- endothelial cells. Without being able to bind the serotonin, the enzyme (indoleamine 2,3-dioxygenase) would
- be unable to destroy it.An excess of tryptophan in the diet, especially with deficiencies of other
- nutrients, can combine with inflammation to increase serotonin. Polyunsaturated fatty acids promote the
- absorption of tryptophan by the brain, and its conversion to serotonin. (A "deficiency" of polyunsaturated
- fat decreases the expression of the enzyme that synthesizes serotonin [McNamara, et al., 2009).Some fruits,
- including bananas, pineapples, and tomatoes, contain enough serotonin to produce physiological effects in
- susceptible people.Besides avoiding foods containing fermentable fibers and starches that resist quick
- digestion, eating fibrous foods that contain antibacterial chemicals, such as bamboo shoots or raw carrots,
- helps to reduce endotoxin and serotonin. Activated charcoal can absorb many toxins, including bacterial
- endotoxin, so it is likely to reduce serotonin absorption from the intestine. Since it can also bind or
- destroy vitamins, it should be used only intermittently. Frolkis, et al. (1989, 1984) found that it extended
- median and average lifespan of rats, beginning in old age (28 months) by 43% and 34%, respectively, when
- given in large quantities (equivalent to about a cup per day for humans) for ten days of each month.The
- amino acid theanine, found in tea, has been reported to decrease the amount of serotonin in the brain,
- probably by decreasing its synthesis and increasing its degradation. This seems to be the opposite of
- the processes in hibernation. Progesterone, thyroid, and niacinamide (not nicotinic acid or inositol
- hexanicotinate) are other safe substances that help to reduce serotonin formation, and/or accelerate its
- elimination. (Niacinamide seems to increase serotonin uptake.)To provide usable energy to the over-stressed
- brain (and heart), R.L. Veech has advocated the use of ketones, but the pure chemicals are expensive to
- make. An easily available and inexpensive source of ketones (in the form of ketoacids, which can be
- converted to amino acids if they aren't needed for energy) is the juice extracted (with a centrifugal
- juicer) from raw potatoes, which also contains proteins and other nutrients. The juice can be scrambled like
- eggs, and is usually tolerated even by very debilitated people.Hypothyroidism is a very common cause of
- increased serotonin (e.g., Henley, et al., 1998), and if the thyroid hormone is supplemented until symptoms
- are resolved, it's likely that the serotonin will have been normalized.<h3>REFERENCES</h3>Vet Rec. 2010 Jan
- 30;166(5):133-6. Effect of diet on plasma tryptophan and serotonin in trained mares and geldings. Alberghina
- D, Giannetto C, Visser EK, Ellis AD. Bull Exp Biol Med. 2005 Jan;139(1):64-7. Effect of serotonin on
- respiration, cerebral circulation, and blood pressure in rats. Aleksandrin VV, Tarasova NN, Tarakanov IA. V.
- V. "Serotonin rapidly decreased local cerebral blood flow (by almost 30%) and blood pressure."Aust N Z J
- Med. 1984 Dec;14(6):888-95. Serotonin antagonists. Anthony M. "The realisation that serotonin plays a role
- not only in the carcinoid syndrome but also in migraine, nociception, dumping syndrome, vascular disease and
- hypertension, has led to an enormous amount of activity in search of serotonin antagonists."Biull Eksp Biol
- Med 1976, 82(10): 1181-3, Role of the biological activity of serotonin in the productin of the "shock lung"
- syndrome, Bazarevich GIa, Deviataev AM, Likhtenshtein AO, Natsvlishvili BP, Sadeko MKh. Headache. 2006
- Sep;46(8):1230-45. Serotonin in trigeminal ganglia of female rodents: relevance to menstrual migraine.Berman
- NE, Puri V, Chandrala S, Puri S, Macgregor R, Liverman CS, Klein RM. Biol Psychiatry. 2000 Mar
- 15;47(6):562-76. Steroid regulation of tryptophan hydroxylase protein in the dorsal raphe of macaques.
- Bethea CL, Mirkes SJ, Shively CA, Adams MR.Bowman, WC & Rand MJ, Textbook of Pharmacology, Second
- ediction. Oxford: Blackwell Scientific Publications, 1980. Arch Int Pharmacodyn Ther. 1962 Jan
- 1;135:142-51. Blockade of depressor responses to serotonin and tryptamine by lysergic acid derivatives in
- the chicken. Bunag RD, Walaszek EJ. J. Theor. Biol. 169:391-402.(1994). Rethinking "shape space":
- evidence from simulated docking suggests that steric shape complementarity is not limiting for
- antibody-antigen recognition and idiotypic interactions. Carneiro, J. and Stewart, J. Psychol Neuropsychiatr
- Vieil. 2010 Dec;8(4):243-54. [Personality and risk of dementia]. [Article in French] Clément JP, Teissier
- MP. Nature Medicine 1995, 1:623-625. The psychobiological regulation of social cooperation, Cloninger
- CR. JAMA. 1962 Jul 28;181:318-21. On migraine headache: serotonin and serotonin antagonism. Dalessio
- DJ. Int Clin Psychopharmacol. 1991 Dec;6 Suppl 3:23-8; discussion 29-31. Depression and 5HT. Deakin JF.
- "Much evidence is compatible with the idea that 5HT systems reduce the impact of impending or actual
- aversive events. Anticipation of an aversive event is associated with anxiety and this motivates avoidance
- behaviour--a normal adaptive response. There is evidence that this is mediated by projections of the dorsal
- raphe nucleus and associated 5HT2 and 5HT3 receptors." Exp Brain Res. 1983;51(1):73-6. Effect of acute
- and chronic 17 beta-estradiol treatment on serotonin and 5-hydroxyindole acetic acid content of discrete
- brain nuclei of ovariectomized rat. Di Paolo T, Diagle M, Picard V, Barden N. "Increased serotonin content
- of the dorsal raphe nucleus and of the substantia nigra were seen following acute (12 h or 24 h)
- administration of 17 beta-estradiol to ovariectomized rats." Neuroscience. 2009 Oct 6;163(2):705-18.
- Epub 2009 Jun 23. Estrogen receptor beta regulates the expression of tryptophan-hydroxylase 2 mRNA within
- serotonergic neurons of the rat dorsal raphe nuclei. Donner N, Handa RJ. Br Med J. 1962 May
- 19;1(5289):1390-1. Carcinoid syndrome: alleviation of diarrhoea and flushing with "Deseril" and Ro 5-1025.
- Dubach UC, Gsell OR. Br. J. Pharmacol Chemother. 1954; 9(1):31-6. Identification of the stable
- antidiuretic substance (stable ADS) of serum with 5-hydroxytryptamine, Erspamer V, Sala G. Brain Res.
- 1996 Mar 4;711(1-2):84-92. In vivo evidence for progesterone dependent decreases in serotonin release in the
- hypothalamus and midbrain central grey: relation to the induction of lordosis. Farmer CJ, Isakson TR, Coy
- DJ, Renner KJ. "The rapid decrease in extracellular 5HT in the MCG suggests that this effect may represent a
- non-genomic action of P." Am J Physiol Endocrinol Metab, 2007;292(4): E1173-E1182, Estrogen potentiates
- adrenocortical responses to stress in female rats, Figueiredo HF, Ulrich-Lai YM, Choi DC, Herman
- JP. Mechanisms of LSD: a glimpse into the serotonergic system, Anne Frederickson,
- 1998,serendip.brynmawr .edu/bb/neuro/neuro98/202s98-paper3/Frederickson3.html. Exp Gerontol.
- 1984;19(4):217-25. Enterosorption in prolonging old animal lifespan. Frolkis VV, Nikolaev VG, Bogatskaya LN,
- Stupina AS, Shcherbitskaya EV, Kovtun AI, Paramonova GI, Sabko VE, Shaposhnikov VM, Rushkevich YuE , et
- al. Biomater Artif Cells Artif Organs. 1989;17(3):341-51. Effect of enterosorption on animal lifespan.
- Frolkis VV, Nikolaev VG, Paramonova GI, Shchorbitskaya EV, Bogatskaya LN, Stupina AS, Kovtun AI, Sabko VE,
- Shaposhnikov VM, Muradian KK, et al. Brit. J. Pharmacol. 1954, 9, 240, Drugs which antagonize
- 5-hydroxytryptamine, Gaddum JH, Hameed KA.Quart J exp Physiol 1953, 121, 15P, Antagonism between lysergic
- acid diethylamide and 5- hydroxytryptamine, Gaddum JH. J Clin Invest. 1983 Jun;71(6):1806-21. Effects
- of parathyroid hormone on skeletal muscle protein and amino acid metabolism in the rat. Garber
- AJ. Synapse. 2011 Mar;65(3):249-56. The microtubule cytoskeleton acts as a key downstream effector of
- neurotransmitter signaling. Gardiner J, Overall R, Marc J. Psychoneuroendocrinology 25: 479-496, 2000.
- Neuroendocrine correlates of temperamental traits in humans, Gerra G, Zaimovic A, Timpano M, Zambelli U,
- Delsignore R, Brambilla F. Br. J. Pharmacol Chemother 1957 Dec;12(4):498-503. The antagonism of the
- vaxcular effects of 50hydroxytryptamine by BOL 148 and sodium salicylate in the human subject. Glover WE,
- Marchall RJ, Whelan RF. "Sodium salicylate is also a specific antagonist of
- 5-hydroxytryptamine....." J. of Psychoactive Drugs 2002, 34(3), p. 266, The serotonergic system and
- mysticism: Could LSD and the nondrug-induced mystical experience share common neural mechanism? Goodman
- N. Pharmacol Biochem Behav. 1996 May;54(1):129-41. Role of 5-HT in stress, anxiety, and depression.
- Graeff FG, Guimarães FS, De Andrade TG, Deakin JF. Med Hypotheses. 2004;62(2):169-72. Biophotons,
- microtubules and CNS, is our brain a "holographic computer"? Grass F, Klima H, Kasper
- S. Pharmacotherapy, 1995; 15(3):357-60. Treatment of depression with cyproheptadine, Greenway SE, Pack
- AT, Greenway FL.J Am Soc Nephrol. 2000 Jun;11(6):1002-7. Effect of serotonin receptor antagonist on
- phosphate excretion. Gross JM, Berndt TJ, Knox FG. Biochem J. 1996 Dec 1;320 ( Pt 2):615-21. Locally
- formed 5-hydroxytryptamine stimulates phosphate transport in cultured opossum kidney cells and in rat
- kidney. Hafdi Z, Couette S, Comoy E, Prie D, Amiel C, Friedlander G. Biological Psychology Volume 51,
- Issue 1, October 1999, Pages 77-81. Harm avoidance and serotonin. Hansenne M, Ansseau M. Physiol Behav.
- 2004 Sep 15;82(2-3):357-68. Anxiety and aggression associated with the fermentation of carbohydrates in the
- hindgut of rats. Hanstock TL, Clayton EH, Li KM, Mallet PE. Endocr Rev. 1980 Fall;1(4):319-38. Biogenic
- amines and the secretion of parathyroid hormone and calcitonin. Heath H 3rd. Rev Neurosci. 2000;11 Spec
- No:213-328. A unifying hypothesis of Alzheimer's disease. IV. Causation and sequence of events. Heininger
- K. Can J Physiol Pharmacol 1998 Dec;76(12):1120-31. Bulbospinal serotonergic activity during changes in
- thyroid status. Henley WN, Bellush LL, Tressler M Biol Psychiatry. 2006 Aug 1;60(3):288-95. Estrogen
- selectively increases tryptophan hydroxylase- 2 mRNA expression in distinct subregions of rat midbrain raphe
- nucleus: association between gene expression and anxiety behavior in the open field. Hiroi R, McDevitt RA,
- Neumaier JF. European Journal of Pharmacology. 1985; 111(2):211-220. Maternal aggression in mice:
- Effects of treatments with PCPA, 5-HTP and 5-HT receptor antagonists. Ieni JR and Thurmond JB. European
- J. Pharmacology 1983, 90:275-78, Raphe neurons-firing rate correlates with size of drug response, Jacobs BL.
- American Scientist 1987, 75:386-91, How hallucinogenic drugs work, Jacobs BL. Arch Gen Psychiatry. 2005
- May;62(5):529-35. The interaction of stressful life events and a serotonin transporter polymorphism in the
- prediction of episodes of major depression: a replication. Kendler KS, Kuhn JW, Vittum J, Prescott CA, Riley
- B. Pharmacol Biochem Behav. 1977 Sep;7(3):245-52. Fatty acid and tryptophan changes on disturbing
- groups of rats and caging them singly. Knott PJ, Hutson PH, Curzon G. Life Sci. 1991;48(2):175-81.
- State-dependent variation in the inhibitory effect of [D-Ala2, D- Leu5]-enkephalin on hippocampal serotonin
- release in ground squirrels. Kramarova LI, Lee TF, Cui Y, Wang LC.Metabolism. 1978 May;27(5):511-20.
- Serotoninergic activation and inhibition: effects on carbohydrate tolerance and plasma insulin and glucagon.
- de Leiva A, Tanenberg RJ, Anderson G, Greenberg B, Senske B, Goetz FC. (In Garattini, Adv in Pharmacol 6,
- pages 131-2, McCullough and Myers, 1965.) J Psychiatr Res. 2009 Mar;43(6):656-63. Omega-3 fatty acid
- deficiency during perinatal development increases serotonin turnover in the prefrontal cortex and decreases
- midbrain tryptophan hydroxylase-2 expression in adult female rats: dissociation from estrogenic effects.
- McNamara RK, Able J, Liu Y, Jandacek R, Rider T, Tso P, Lipton JW. Pharmacol Biochem Behav. 1976
- Jul;5(1):55-61. The role of serotonergic pathways in isolation- induced aggression in mice.Malick JB,
- Barnett A. "All of the antiserotonergic drugs selectively antagonized the fighting behavior of the isolated
- mice...." Curr Dev Psychopharmacol. 1979;5:1-27. The pharmacology of isolation-induced aggressive
- behavior in mice. Malick JB.J Geriatr Psychiatry Neurol. 1997 Jan;10(1):29-32. Neurodegeneration, sleep, and
- cerebral energy metabolism: a testable hypothesis. Mamelak M. Vopr Med Khim. 1991 Sep-Oct;37(5):2-6.
- [The role of monoamine oxidase in the regulation of mitochondrial energy functions]. Medvedev AE, Gorkin
- VZ. Vopr Med Khim. 1990 Sep-Oct;36(5):18-21. [Regulation by biogenic amines of energy functions of
- mitochondria]. [Article in Russian] Medvedev AE. Diabetes. 2004 Jan;53(1):14-20. Portal serotonin
- infusion and glucose disposal in conscious dogs. Moore MC, Geho WB, Lautz M, Farmer B, Neal DW, Cherrington
- AD. Neuropsychobiology 1996; 34:155-165, Serotonin and dopamine as mediators of sensation seeking
- behavior, Netter P, Henning J, Roed IS. Comp Biochem Physiol C Toxicol Pharmacol. 2002
- Dec;133(4):507-13. Comparative biology and pathology of oxidative stress in Alzheimer and other
- neurodegenerative diseases: beyond damage and response. Perry G, Taddeo MA, Nunomura A, Zhu X, Zenteno-Savin
- T, Drew KL, Shimohama S, Avila J, Castellani RJ, Smith MA.Pharmacol Biochem Behav. 1993 Sep;46(1):9-13.
- Involvement of brain tryptophan hydroxylase in the mechanism of hibernation. Popova NK, Voronova IP, Kulikov
- AV. Pharmacol Biochem Behav. 1981 Jun;14(6):773-7. Brain serotonin metabolism in hibernation. Popova
- NK, Voitenko NN. Biol Psychiatry 42: 1123-1129, 1997, Clomipramine challenge responses covary with
- Tridimensional Personality Questionnaire scores in healthy subjects, Ruegg RG, Gilmore J, Ekstrom RD,
- Corrigin M, Knight B, et al. J Psychopharmacol. 2010 May;24(5):725-31. Epub 2009 Nov 25. Social
- separation and diazepam withdrawal increase anxiety in the elevated plus-maze and serotonin turnover in the
- median raphe and hippocampus. dos Santos L, de Andrade TG, Graeff FG. Res Commun Chem Pathol Pharmacol
- 1975 Jan;10(1):37-50. Thyroid hormone control of serotonin in developing rat brain.Schwark WS, Keesey RR.
- "Experimental cretinism, induced by daily propylthiouracil treatment starting at birth, caused increased
- serotonin levels in all brain regions studied." Neurology. 2006 Jun 27;66(12):1920-2. Cluster headache
- research, Sewell RA, Halpern JH, Pope HG. Cerebral Cortex 2010 Nov;20(11):2560-7. Estrogen promotes stress
- sensitivity in a prefrontal cortex-amygdala pathway,Shansky RM, Hamo C, Hof PR, Lou W, McEwen BS, Morrison
- JH. Scand J Clin Lab Invest. 2004;64(1):3-8. Platelet serotonin 5-HT2A receptor binding in patients
- with carcinoid tumor. Spigset O, Kristoffersson A, Mjörndal T. Science 1979, 205:515-18, Dissociations
- between the effects of LSD on behavior and raphe unit activity in freely moving cats, Trulson ME &
- Jacobs BL. Neurobiol Aging. 1985 Summer;6(2):107-11. Synergistic effects of estrogen and serotonin-
- receptor agonists on the development of pituitary tumors in aging rats. Walker RF, Cooper RL.Biosci
- Biotechnol Biochem. 1998 Apr;62(4):816-7. Theanine-induced reduction of brain serotonin concentration in
- rats.Yokogoshi H, Mochizuki M, Saitoh K.Biosci Biotechnol Biochem. 1995 Apr;59(4):615-8. Reduction effect of
- theanine on blood pressure and brain 5-hydroxyindoles in spontaneously hypertensive rats. Yokogoshi H, Kato
- Y, Sagesaka YM, Takihara-Matsuura T, Kakuda T, Takeuchi N. J Clin Endocrinol Metab. 1980
- Dec;51(6):1274-8. Serotonin stimulates adenosine 3',5'- monophosphate accumulation in parathyroid adenoma.
- Zimmerman D, Abboud HE, George LE, Edis AJ, Dousa TP.Neurosci Biobehav Rev. 1990 Winter;14(4):507-10.
- 5-HT-related drugs and human experimental anxiety. Zuardi AW.
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