Serotonin
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Do you have any studies to confirm serotonin=bad?
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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.
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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.
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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.
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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.
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Preparation for Lysergic Acid Amides: United States Patent Office 2,736,728 Patented February 28, 1956 Richard P. Pioch, Indianapolis, Indiana, assignor, to Eli Lilly and Co., Indianapolis, Indiana, a corporation of Indiana. No drawing. Application December 6, 1954, Serial No. 473,443. 10 claims. (Cl. 260-285.5)
From the PDR on Prozac: “Pharmacodynamics: The antidepressant and antiobsessive-compulsive action of fluoxetine is presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. Studies at clinically relevant doses in man have demonstrated that fluoxetine blocks the uptake of serotonin into human platelets. Studies in animals also suggest that fluoxetine is a much more potent uptake inhibitor of serotonin than of norepinephrine.”
The Lancet 269 (1955): 117–20. “Reserpine in the Treatment of Anxious and Depressed Patients,” Davies DL and Shepherd M.
Gen Pharmacol 1994 Oct;25(6):1257-1262. Serotonin-induced decrease in brain ATP, stimulation of brain anaerobic glycolysis and elevation of plasma hemoglobin; the protective action of calmodulin antagonists. Koren-Schwartzer N, Chen-Zion M, Ben-Porat H, Beitner R Department of Life Sciences, Bar-Ilan University, Ramat Gan, Israel. 1. Injection of serotonin (5-hydroxytryptamine) to rats, induced a dramatic fall in brain ATP level, accompanied by an increase in P(i). Concomitant to these changes, the activity of cytosolic phosphofructokinase, the rate-limiting enzyme of glycolysis, was significantly enhanced. Stimulation of anaerobic glycolysis was also reflected by a marked increase in lactate content in brain. 2. Brain glucose 1,6-bisphosphate level was decreased, whereas fructose 2,6-bisphosphate was unaffected by serotonin. 3. All these serotonin-induced changes in brain, which are characteristic for cerebral ischemia, were prevented by treatment with the calmodulin (CaM) antagonists, trifluoperazine or thioridazine. 4. Injection of serotonin also induced a marked elevation of plasma hemoglobin, reflecting lysed erythrocytes, which was also prevented by treatment with the CaM antagonists. 5. The present results suggest that CaM antagonists may be effective drugs in treatment of many pathological conditions and diseases in which plasma serotonin levels are known to increase.
J Neural Transm 1998;105(8-9):975-86. Role of tryptophan in the elevated serotonin-turnover in hepatic encephalopathy. Herneth AM, Steindl P, Ferenci P, Roth E, Hortnagl H Department of Internal Medicine IV, Gastroenterology and Hepatology, University of Vienna, Austria. The increase of the brain levels of 5-hydroxyindoleacetic acid (5-HIAA) in hepatic encephalopathy (HE) suggests an increased turnover of serotonin (5-HT). To study the role of tryptophan on the increased brain 5-HT metabolism in HE, we attempted to monitor brain levels of tryptophan in rats with thioacetamide-induced acute liver failure by intravenous infusion of branched-chain amino acids (BCAA). The effect of this treatment on 5-HT synthesis and metabolism was investigated in five brain areas. BCAA-infusions (1 and 2 gm/kg/24 h) increased the ratio BCAA/aromatic amino acids in plasma two- and fourfold, respectively, and lowered both plasma and brain levels of tryptophan. At the higher BCAA-dose all parameters suggesting an altered brain 5-HT metabolism (increased brain levels of 5-HT and 5-HIAA, increased 5-HIAA/5-HT ratio) were almost completely normalized. These results provide further evidence for the role of tryptophan in the elevation of brain 5-HT metabolism and for a potential role of BCAA in the treatment of HE.
Tugai VA; Kurs'kii MD; Fedoriv OM. [Effect of serotonin on Ca2+ transport in mitochondria conjugated with the respiratory chain]. Ukrainskii Biokhimicheskii Zhurnal, 1973 Jul-Aug, 45(4):408-12.
Kurskii MD; Tugai VA; Fedoriv AN. [Effect of serotonin and calcium on separate components of respiratory chain of mitochondria in some rabbit tissues]. Ukrainskii Biokhimicheskii Zhurnal, 1970, 42(5):584-8.
Watanabe Y; Shibata S; Kobayashi B. Serotonin-induced swelling of rat liver mitochondria. Endocrinologia Japonica, 1969 Feb, 16(1):133-47.
Mahler DJ; Humoller FL. The influence of serotonin on oxidative metabolism of brain mitochondria. Proceedings of the Society for Experimental Biology and Medicine, 1968 Apr, 127(4):1074-9.
Eur J Pharmacol 1994 Aug 11;261(1-2):25-32. The effect of alpha 2-adrenoceptor antagonists in isolated globally ischemic rat hearts. Sargent CA, Dzwonczyk S, Grover G.J. “The alpha 2-adrenoceptor antagonist, yohimbine, has been reported to protect hypoxic myocardium. Yohimbine has several other activities, including 5-HT receptor antagonism, at the concentrations at which protection was found.” “Pretreatment with yohimbine (1-10 microM) caused a concentration-dependent increase in reperfusion left ventricular developed pressure and a reduction in end diastolic pressure and lactate dehydrogenase release. The structurally similar compound rauwolscine (10 microM) also protected the ischemic myocardium. In contrast, idozoxan (0.3-10 microM) or tolazoline (10 microM) had no protective effects. The cardioprotective effects of yohimbine were partially reversed by 30 microM 5-HT. These results indicate that the mechanism for the cardioprotective activity of yohimbine may involve 5-HT receptor antagonistic activity.”
Zubovskaia AM. [Effect of serotonin on some pathways of oxidative metabolism in the mitochondria of rabbit heart muscle]. Voprosy Meditsinskoi Khimii, 1968 Mar-Apr, 14(2):152-7.
Warashina Y. [On the effect of serotonin on phosphorylation of rat liver mitochondria]. Hoppe-Seylers Zeitschrift fur Physiologische Chemie, 1967 Feb, 348(2):139-48.
Eur Neuropsychopharmacol 1997 Oct;7 Suppl 3:S323-S328. Prevention of stress-induced morphological and cognitive consequences. McEwen BS, Conrad CD, Kuroda Y, Frankfurt M, Magarinos AM, McKittrick C, Laboratory of Neuroendocrinology, Rockefeller University, New York, NY 10021, USA. Atrophy and dysfunction of the human hippocampus is a feature of aging in some individuals, and this dysfunction predicts later dementia. There is reason to believe that adrenal glucocorticoids may contribute to these changes, since the elevations of glucocorticoids in Cushing's syndrome and during normal aging are associated with atrophy of the entire hippocampal formation in humans and are linked to deficits in short-term verbal memory. We have developed a model of stress-induced atrophy of the hippocampus of rats at the cellular level, and we have been investigating underlying mechanisms in search of agents that will block the atrophy. Repeated restraint stress in rats for 3 weeks causes changes in the hippocampal formation that include suppression of 5-HT1A receptor binding and atrophy of dendrites of CA3 pyramidal neurons, as well as impairment of initial learning of a radial arm maze task. Because serotonin is released by stressors and may play a role in the actions of stress on nerve cells, we investigated the actions of agents that facilitate or inhibit serotonin reuptake. Tianeptine is known to enhance serotonin uptake, and we compared it with fluoxetine, an inhibitor of 5-HT reuptake, as well as with desipramine. Tianeptine treatment (10 mg/kg/day) prevented the stress-induced atrophy of dendrites of CA3 pycamidal neurons, whereas neither fluoxetine (10 mg/kg/day) nor desipramine (10 mg/kg/day) had any effect. Tianeptine treatment also prevented the stress-induced impairment of radial maze learning. Because corticosterone- and stress-induced atrophy of CA3 dendrites is also blocked by phenytoin, an inhibitor of excitatory amino acid release and actions, these results suggest that serotonin released by stress or corticosterone may interact pre- or post-synaptically with glutamate released by stress or corticosterone, and that the final common path may involve interactive effects between serotonin and glutamate receptors on the dendrites of CA3 neurons innervated by mossy fibers from the dentate gyrus. We discuss the implications of these findings for treating cognitive impairments and the risk for dementia in the elderly.
J Mol Cell Cardiol 1985 Nov;17(11):1055-63. Digitoxin therapy partially restores cardiac catecholamine and brain serotonin metabolism in congestive heart failure. Sole MJ, Benedict CR, Versteeg DH, de Kloet ER. The effect of therapeutic doses of digitalis in modifying neural activity has been the subject of considerable controversy. In earlier studies we reported an increase both in serotonergic activity in the posterior hypothalamus and pons-medulla and in cardiac sympathetic tone in the failing cardiomyopathic hamster. In this study we examine the effects of doses of digitoxin, known to be therapeutic for hamster heart failure, on monoamine neurotransmitter metabolism in the brain and heart during the cardiomyopathy. Both digitoxin and ASI-222, a polar amino-glycoside which does not cross the blood-brain barrier, given either acutely (6 mg/kg ip) or chronically (2 mg/kg/day ip for 10 days), normalized the failure-induced increase in serotonin turnover in the pons-medulla but had no effect on the changes in the posterior hypothalamus. Digitoxin therapy also reduced cardiac and adrenal sympathetic activity partially restoring cardiac catecholamine stores. In order to more clearly define the pathways involved we measured serotonin (microgram/g protein) in 18 brain nuclei after 10 days of digitoxin or vehicle treatment. Heart failure was associated with an increase in serotonin in five nuclei: the mammillary bodies, ventromedial, periventricular and paraventricular nuclei of the hypothalamus, and the centralis superior nucleus of the raphe. Digitoxin therapy completely normalized the changes in the centralis superior and ventromedialis nuclei; neither congestive heart failure nor digitoxin affected serotonin levels in other nuclei. We conclude that there is an increase in activity in specific brain serotonergic nuclei in congestive heart failure. Digitalis reduces cardiac sympathetic tone and restores the changes in two of these nuclei: the ventromedial and the centralis superior.+2
Brain Res 2000 Jan 24;853(2):275-81. Duration and distribution of experimental muscle hyperalgesia in humans following combined infusions of serotonin and bradykinin. Babenko V, Svensson P, Graven-Nielsen T, Drewes AM, Jensen TS, Arendt-Nielsen L.
Eur J Pharmacol 1992 Feb 25;212(1):73-8. 5-HT3 receptor antagonists reverse helpless behaviour in rats. Martin P, Gozlan H, Puech AJ Departement de Pharmacologie, Faculte de Medecine Pitie-Salpetriere, Paris, France. The effects of the 5-HT3 receptor antagonists, zacopride, ondansetron and ICS 205-930, were investigated in an animal model of depression, the learned helplessness test. Rats previously subjected to a session of 60 inescapable foot-shocks exhibited a deficit of escape performance in three subsequent shuttle-box sessions. The 5-HT3 receptor antagonists administered i.p. twice daily on a chronic schedule (zacopride 0.03-2 mg/kg per day; ondansetron and ICS 205-930: 0.125-2 mg/kg per day) reduced the number of escape failures at low to moderate daily doses. This effect was not observed with the highest dose(s) of zacopride, ondansetron and ICS 205-930 tested. These results indicate that 5-HT3 antagonists may have effects like those of conventional antidepressants in rats.
Neuropharmacology 1992 Apr;31(4):323-30. Presynaptic serotonin mechanisms in rats subjected to inescapable shock. Edwards E, Kornrich W, Houtten PV, Henn FA. “After exposure to uncontrollable shock training, two distinct groups of rats can be defined in terms of their performance in learning to escape from a controllable stress. Learned helpless rats do not learn to terminate the controllable stress, whereas non-learned helpless rats learn this response as readily as naive control rats do.” “These results implicate presynaptic serotonin mechanisms in the behavioral deficit caused by uncontrollable shock. In addition, a limbic-hypothalamic pathway may serve as a control center for the behavioral response to stress.”
Neurochem Int 1992 Jul;21(1):29-35. In vitro neurotransmitter release in an animal model of depression. Edwards E, Kornrich W, van Houtten P, Henn FA. “Sprague-Dawley rats exposed to uncontrollable shock can be separated by a subsequent shock escape test into two groups: a "helpless" (LH) group which demonstrates a deficit in escape behavior, and a "nonlearned helpless" (NLH) group which shows no escape deficit and acquires the escape response as readily as naive control rats (NC) do.” “The major finding concerned a significant increase in endogenous and K(+)-stimulated serotonin (5-HT) release in the hippocampal slices of LH rats. There were no apparent differences in acetylcholine, dopamine and noradrenaline release in the hippocampus of LH rats as compared to NLH and NC rats. These results add further support to previous studies in our laboratory which implicate presynaptic 5-HT mechanisms in the behavioral deficit caused by uncontrollable shock.”
Psychiatry Res 1994 Jun;52(3):285-93. In vivo serotonin release and learned helplessness. Petty F, Kramer G, Wilson L, Jordan S Mental Health Clinic, Dallas Veterans Affairs Medical Center, TX. Learned helplessness, a behavioral depression caused by exposure to inescapable stress, is considered to be an animal model of human depressive disorder. Like human depression, learned helplessness has been associated with a defect in serotonergic function, but the nature of this relationship is not entirely clear. We have used in vivo microdialysis brain perfusion to measure serotonin (5-hydroxytryptamine, 5HT) in extracellular space of medial frontal cortex in conscious, freely moving rats. Basal 5HT levels in rats perfused before exposure to tail-shock stress did not themselves correlate with subsequent learned helplessness behavior. However, 5HT release after stress showed a significant increase with helpless behavior. These data support the hypothesis that a cortical serotonergic excess is causally related to the development of learned helplessness.
Pharmacol Biochem Behav 1994 Jul;48(3):671-6. Does learned helplessness induction by haloperidol involve serotonin mediation? Petty F, Kramer G, Moeller M Veterans Affairs Medical Center, Dallas 75216. Learned helplessness (LH) is a behavioral depression following inescapable stress. Helpless behavior was induced in naive rats by the dopamine D2 receptor blocker haloperidol (HDL) in a dose-dependent manner, with the greatest effects seen at 20 mg/kg (IP). Rats were tested 24 h after injection. Haloperidol (IP) increased release of serotonin (5-HT) in medial prefrontal cortex (MPC) as measured by in vivo microdialysis. Perfusion of HDL through the probe in MPC caused increased cortical 5-HT release, as did perfusion of both dopamine and the dopamine agonist apomorphine. Our previous work found that increased 5-HT release in MPC correlates with the development of LH. The present work suggests that increased DA release in MPC, known to occur with both inescapable stress and with HDL, may play a necessary but not sufficient role in the development of LH. Also, this suggests that increased DA activity in MPC leads to increased 5-HT release in MPC and to subsequent behavioral depression.
Stroke 1991 Nov;22(11):1448-51. Platelet secretory products may contribute to neuronal injury. Joseph R, Tsering C, Grunfeld S, Welch KM Department of Neurology, Henry Ford Hospital and Health Sciences Center, Detroit, MI 48202. BACKGROUND: We do not fully understand the mechanisms for neuronal damage following cerebral arterial occlusion by a thrombus that consists mainly of platelets. The view that certain endogenous substances, such as glutamate, may also contribute to neuronal injury is now reasonably well established. Blood platelets are known to contain and secrete a number of substances that have been associated with neuronal dysfunction. Therefore, we hypothesize that a high concentration (approximately several thousand-fold higher than in plasma, in our estimation) of locally released platelet secretory products derived from the causative thrombus may contribute to neuronal injury and promote reactive gliosis. SUMMARY OF COMMENT: We have recently been able to report some direct support for this concept. When organotypic spinal cord cultures were exposed to platelet and platelet products, a significant reduction in the number and the size of the surviving neurons occurred in comparison with those in controls. We further observed that serotonin, a major platelet product, has neurotoxic properties. There may be other platelet components with similar effect. CONCLUSIONS: The hypothesis of platelet-mediated neurotoxicity gains some support from these recent in vitro findings. The concept could provide a new area of research in stroke, both at the clinical and basic levels.
J. Clin Psychopharmacol 1991 Aug; 11(4):277-9. Disseminated intravascular coagulation and acute myoglobinuric renal failure: a consequence of the serotonergic syndrome. Miller F, Friedman R, Tanenbaum J, Griffin A. Letter
Chronobiol Int 2000 Mar;17(2):155-72. Association of the antidiabetic effects of bromocriptine with a shift in the daily rhythm of monoamine metabolism within the suprachiasmatic nuclei of the Syrian hamster. Luo S, Luo J, Cincotta AH. “Bromocriptine, a dopamine D2 agonist, inhibits seasonal fattening and improves seasonal insulin resistance in Syrian hamsters.” “Compared with control values, bromocriptine treatment significantly reduced weight gain (14.9 vs. -2.9 g, p < .01) and the areas under the GTT glucose and insulin curves by 29% and 48%, respectively (p < .05). Basal plasma insulin concentration was markedly reduced throughout the day in bromocriptine-treated animals without influencing plasma glucose levels. Bromocriptine reduced the daily peak in FFA by 26% during the late light span (p < .05).” “Thus, bromocriptine-induced resetting of daily patterns of SCN neurotransmitter metabolism is associated with the effects of bromocriptine on attenuation of the obese insulin-resistant and glucose-intolerant condition. A large body of corroborating evidence suggests that such bromocriptine-induced changes in SCN monoamine metabolism may be functional in its effects on metabolism.”
Eur J Pharmacol 1982 Jul 30;81(4):569-76. Actions of serotonin antagonists on dog coronary artery. Brazenor RM, Angus JA. Serotonin released from platelets may initiate coronary vasospasm in patients with variant angina. If this hypothesis is correct, serotonin antagonists without constrictor activity may be useful in this form of angina. We have investigated drugs classified as serotonin antagonists on dog circumflex coronary artery ring segments in vitro. Ergotamine, dihydroergotamine, bromocriptine, lisuride, ergometrine, ketanserin, trazodone, cyproheptadine and pizotifen caused non-competitive antagonism of serotonin concentration-response curves. In addition, ketanserin, trazodone, bromocriptine and pizotifen inhibited noradrenaline responses in concentrations similar to those required for serotonin antagonism. All drugs with the exception of ketanserin, cyproheptadine and pizotifen showed some degree of intrinsic constrictor activity. Methysergide antagonized responses to serotonin competitively but also constricted the coronary artery. The lack of a silent competitive serotonin antagonist precludes a definite characterization of coronary serotonin receptors at this time. However, the profile of activity observed for the antagonist drugs in the coronary artery differs from that seen in other vascular tissues. Of the drugs tested, ketanserin may be the most useful in variant angina since it is a potent 5HT antagonist, lacks agonist activity and has alpha-adrenoceptor blocking activity.
Eur J Pharmacol 1985 May 8;111(2):211-20. Maternal aggression in mice: effects of treatments with PCPA, 5-HTP and 5-HT receptor antagonists. Ieni JR, Thurmond JB. Drug treatments which influence brain serotonergic systems were administered to lactating female mice during the early postpartum period, and their effects on aggressive behavior, locomotor activity and brain monoamines were examined. P-chlorophenylalanine (200 and 400 mg/kg) and 5-hydroxytryptophan (100 mg/kg) inhibited fighting behavior of postpartum mice toward unfamiliar male intruder mice. These drug-treated postpartum females showed increased latencies to attack male intruders and also reduced frequencies of attack. In addition, postpartum mice treated with the serotonin receptor antagonists, mianserin (2 and 4 mg/kg), methysergide (4 mg/kg) and methiothepin (0.25 and 0.5 mg/kg), displayed significantly less aggressive behavior than control mice, as measured by reduced number of attacks. Whole brain monoamine and monoamine metabolite levels were measured after drug treatments. The behavioral results are discussed in terms of drug-induced changes in brain chemistry and indicate a possible role for serotonin in the mediation of maternal aggressive behavior of mice.
Naunyn Schmiedebergs Arch Pharmacol 1987 Apr;335(4):454-64. Effects of gepirone, an aryl-piperazine anxiolytic drug, on aggressive behavior and brain monoaminergic neurotransmission. McMillen BA, Scott SM, Williams HL, Sanghera MK. Gepirone (BMY 13805), a buspirone analog, was used to determine the antianxiety mechanism of the arylpiperazine class of drugs. Because of the weak effects of these drugs on conflict behavior, isolation-induced aggressive mice were used as the antianxiety model. Gepirone, like buspirone, potently inhibited attacks against group housed intruder mice (ED50 = 4.5 mg/kg i.p.) without causing sedation or ataxia. Inhibition of aggression was potentiated by co-administration of 0.25 mg/kg methiothepin or 2.5 mg/kg methysergide. Gepirone had variable effects on dopamine metabolism and reduced 5-hydroxytryptamine (5HT) metabolism about one third after a dose of 2.5 mg/kg. In contrast to buspirone, which markedly increased dopaminergic impulse flow, gepirone inhibited the firing of most cells recorded from the substantia nigra zona compacta in doses of 2.3-10 mg/kg i.v. and the effects were reversible by administration of haloperidol. The common metabolite of buspirone and gepirone, 1-(2-pyrimidinyl)-piperazine, caused increased firing rates only. Gepirone potently inhibited serotonergic impulse flow recorded from the dorsal raphe nucleus (88.3% after 0.04 mg/kg) and this effect was partially reversed by serotonergic antagonists. Both buspirone and gepirone displaced [3H]-5HT from the 5HT1a binding site in the hippocampus with IC50 values of 10 and 58 nM, respectively. Non-alkyl substituted aryl-piperazines displaced [3H]-5HT from both 5HT1a and 5HT1b binding sites. Thus, although gepirone may be a weak postsynaptic 5HT agonist, its primary effect is to decrease 5HT neurotransmission. In support of this conclusion was the observed potentiation of antiaggressive effects by blocking 5HT receptors wit small doses of methiothepin or methysergide, which would exacerbate the decreased release of 5HT caused by gepirone. These results are in harmony with reports that decreased serotonergic activity has anxiolytic-like effects in animal models of anxiety.
Farmakol Toksikol 1975 Mar-Apr;38(2):148-51. [Participation of the serotonin-reactive brain structure in certain forms of behavior in golden hamsters]. Popova NK, Bertogaeva VD. A viviacious play of young hamsters is shown to be accompanied by a drop of the serotonin level in the brain stem and the subsequent slumber - by its rise, while the corticosteroids content of the peripheral blood with the playful behavior experiences no changes. Iprazid and 5-oxytryptophan inhibit the playful activity, while dioxyphenylalanina (DOPA) does not influence it. A similar depression of the serotonin level in the brain stem was also noted in an aggressive behavior and stress conditions arising when adult male-hamsters are grouped together. A conclusion is drawn to the effect that changes in the content of serotonin in the brain stem are not associated with the emotional colouration of the condition, but rather reflect the transition from the somnolence to a highly active behavior.
Biol Psychiatry 1985 Sep;20(9):1023-5 Triiodothyronine-induced reversal of learned helplessness in rats. Martin P, Brochet D, Soubrie P, Simon P. -
It's probably still bad to reduce this to 'serotonin=bad' though. It probably can't be sustainably minimised without holistic improvement. But acute antagonism of release or receptor can be therapeutic.
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@ThinPicking jinxies ;))
@lactose rtfm http://raypeat.com/articles/ -
Is Serotonin An Upper Or A Downer is by far the best overview of the topic Ive read, it should be essential reading for any Peater:
https://pubmed.ncbi.nlm.nih.gov/25625874/you can find the full article on sci-hub
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If you read any recent studies about serotonin, especially when related to TPH1 inhibition. You will find that the role of THP1-generated serotonin is accepted in the pathology of obesity, IBS, IBD, osteoporosis, diabetes, inflammation, fibrosis and some cancers.
THP2-generated serotonin is still considered good
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10447248/
Activation of brown adipose tissue (BAT) in humans is a strategy to treat obesity and metabolic disease. Here we show that the serotonin transporter (SERT), encoded by SLC6A4, prevents serotonin-mediated suppression of human BAT function. RNA sequencing of human primary brown and white adipocytes shows that SLC6A4 is highly expressed in human, but not murine, brown adipocytes and BAT. Serotonin decreases uncoupled respiration and reduces uncoupling protein 1 via the 5-HT2B receptor. SERT inhibition by the selective serotonin reuptake inhibitor (SSRI) sertraline prevents uptake of extracellular serotonin, thereby potentiating serotonin’s suppressive effect on brown adipocytes. Furthermore, we see that sertraline reduces BAT activation in healthy volunteers, and SSRI-treated patients demonstrate no 18F-fluorodeoxyglucose uptake by BAT at room temperature, unlike matched controls. Inhibition of BAT thermogenesis may contribute to SSRI-induced weight gain and metabolic dysfunction, and reducing peripheral serotonin action may be an approach to treat obesity and metabolic disease.
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UCP1 activation is also one of the pathways thought of that methionine restriction causes lifespan extension:
