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July 20, 1979, Vol 36, No. 8 >
Article | July 20, 1979

Asymmetry and Mood, Emergent Properties of Serotonin Regulation: Title and subTitle BreakA Proposed Mechanism of Action of Lithium

Arnold J. Mandell, MD; Suzanne Knapp, MS
Arch Gen Psychiatry. 1979;36(8):909-916. doi:10.1001/archpsyc.1979.01780080083019
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Comments

The purpose of this communication is to develop a model of the pathogenesis of affective spectrum disorders and their treatment and prevention with lithium; the model is based on (1) studies of baseline and drug-induced bilateral asymmetry in tryptophan and serotonin levels in rat brain mesostriatal and mesolimbic systems, (2) singlecell quantitative histochemical determinations of serotonin content in lateral median and dorsal raphe nuclei, (3) the responses of brain tryptophan hydroxylase activity to psychotropic agents, (4) in vitro studies of the kinetic properties of tryptophan hydroxylase, and (5) evidence of lateral affective specialization in human brain. The disorders are construed as diseases of regulation involving an abnormal form of brain tryptophan hydroxylase with hyperbolic substrate kinetics, possibly resulting from a hereditary defect in enzyme cooperativity or calcium metabolism or the influence of yet unidentified ligands. The abnormal enzyme kinetics would serve to amplify the functional impact of existing bilateral asymmetries

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Aghajanian GK, Wang RY:  Physiology and pharmacology of central serotonergic neurons , in Lipton MA, DiMascio A, Killam KF (eds): Psychopharmacology: A Generation of Progress . New York, Raven Press, 1978;, pp 171-184.
2 +
Davis M, Sheard MH:  Habituation and sensitization of the rat startle response: Effects of raphe lesions . Physiol Behav 12:425-431, 1974;.
3 +
Jouvet M:  Biogenic amines and the states of sleep . Science 163:32-39, 1969;.
4 +
Myers RD, Beleshin DB:  Changes in serotonin release in hypothalamus during cooling or warming of the monkey . Am J Physiol 220:1746-1753, 1971;.
5 +
Lints CE, Harvey JA:  Altered sensitivity to footshock and decreased brain content of serotonin following brain lesions in the rat . J Comp Physiol Psychol 67:23-31, 1969;.
6 +
Conner RL, Stolk JM, Barchas JD, et al:  The effect of p-chlorophenylalanine (PCPA) on shock-induced fighting behavior in rats . Physiol Behav 5:1221-1234, 1970;.
7 +
Fibiger HC, Campbell BA:  The effect of parachlorophenylalanine on spontaneous locomotor activity in the rat . Neuropharmacology 10:25-32, 1971;.
8 +
Wise CD, Berger BD, Stein L:  Serotonin: A possible mediator of behavioral suppression induced by anxiety . Dis Nerv Syst 31( (suppl) ):34-37, 1970;.
9 +
Meyerson BJ:  Central nervous monoamines and hormone induced estrus behavior in the spayed rat . Acta Physiol Scand 63( (suppl 241) ):1-32, 1964;.
10 +
Woolley DW:  A method for demonstration of the effects of serotonin on learning ability , in Mikhel'son M Ya, Lougo VG (eds): Pharmacology of Conditioning, Learning and Retention . Oxford, Pergamon Press, 1965;, pp 231-236.
11 +
Panksepp J, Nance DM:  Effects of para-chlorophenylalanine on food intake in rats . Physiol Psychol 2:360-364, 1974;.
12 +
Sailer CF, Stricker EM:  Hyperphagia and increased growth after intraventricular injection of 5,7-dihydroxytryptamine . Science 192:385-387, 1976;.
13 +
Geyer MA, Puerto A, Menkes DB, et al:  Behavioral studies following lesions of the mesolimbic and mesostriatal serotonergic pathways . Brain Res 106:257-270, 1976;.
14 +
Hollister AS, Breese GR, Kuhn CM, et al:  An inhibitory role for brain serotonin-containing systems in the locomotor effects of d-amphetamine . J Pharmacol Exp Ther 198:12-21, 1976;.
15 +
Isaacson RL, Wickelgren WO:  Hippocampal ablation and passive avoidance . Science 138:1104-1106, 1962;.
16 +
Essman WB:  Enhanced memory consolidation with drug-induced regional changes in brain RNA and serotonin metabolism . Pharmakopsychiatr Neuropsychopharmakol 2:28-34, 1969;.
17 +
Stein D, Jouvet M, Pujol JF:  Effects of a-methyl-p-tyrosine upon cerebral amine metabolism and sleep states in the cat . Brain Res 72:360-365, 1974;.
18 +
Hobson JA, McCarley RW, Wysinski PW:  Sleep cycle oscillation: Reciprocal discharge by two brain stem neuronal groups . Science 189:55-58, 1975;.
19 +
Fuxe K:  Evidence for the existence of monoamine neurons in the central nervous system: III. The monoamine nerve terminal . Z Zellforsch 65:572-596, 1965;.
20 +
Naumenko EV:  Hypothalamic chemoreactive structures and the regulation of pituitary-adrenal function . Brain Res 11:1-10, 1968;.
21 +
Bunney WE, Mason JW, Roatch JF:  A psychoendocrine study of severe psychotic depressive crisis . Am J Psychiatry 122:72-80, 1965;.
22 +
Van Praag HM:  Depressie en de stofunsseling van 5-hydroxytryptamine . Ned Tijdschr Geneeskd 113:2245-2247, 1969;.
23 +
Gershon ES, Targum SD, Kessler LR, et al:  Genetic studies and biological strategies in the affective disorders . Prog Med Genet 2:101-164, 1977;.
24 +
Azmitia EC, Buchan AM, Williams JH:  Structural and functional restoration by collateral sprouting of hippocampal 5-HT axons . Nature 274:374-376, 1978;.
25 +
Coppen A, Prange AJ Jr, Whybrow PC, et al:  Abnormalities of indoleamines in affective disorders . Arch Gen Psychiatry 26:474-478, 1972;.
26 +
Asberg M, Thoren P, Traskman L, et al:  Serotonin depression: A biochemical subgroup within the affective disorders . Science 191:478-480, 1976;.
27 +
Van Praag HM, Korf J, Schut D:  Cerebral monoamines and depression . Arch Gen Psychiatry 28:827-831, 1973;.
28 +
Goodwin FK, Extein IL, Wehr TA:  Some recent advances in psychobiology and psychopharmacology of affective disorders , in Ayd FJ, Taylor IJ (eds): Mood Disorders: The World's Major Public Health Problem . Baltimore, Ayd Medical Communications, 1978;, pp 22-43.
29 +
Harnad S, Doty RW, Goldstein L, et al (eds): Lateralization in the Nervous System . New York, Academic Press Inc, 1977;.
30 +
Mandell AJ, Knapp S:  Regulatory properties of tryptophan hydroxylase determine the degree of bilateral asymmetry in mesolimbic serotonin synthesis: A model for mood control . Fed Proc , to be published.
31 +
Mandell AJ:  Toward a psychobiology of transcendence: God in the brain , in Davidson JM, Davidson RJ (eds): The Psychobiology of Consciousness . New York, Plenum Press Inc, to be published.
32 +
Mandell AJ, Knapp S, Geyer MA:  Lithium decreases and cocaine increases the bilateral asymmetry of serotonin in mesostriatal and mesolimbic systems associated with changes in the kinetic properties of tryptophan hydroxylase , in Usdin E (ed): Catecholamines: Basic and Clinical Frontiers . New York, Pergamon Press, to be published.
33 +
Knapp S, Mandell AJ:  Conformational influences on brain tryptophan hydroxylase activity by submicromolar calcium: opposite effects of equimolar lithium . J Neural Transm , to be published.
34 +
Weinstein EA, Kahn RC: Denial of Illness: Symbolic and Physiological Aspects . Springfield, Ill, Charles C Thomas Publisher, 1955;.
35 +
Terzian H:  Behavioral and EEG effects of intracarotid sodium amytal injections . Acta Neurochir 12:230-240, 1964;.
36 +
Gainotti G:  Emotional behavior and hemispheric side of the lesion . Cortex 8:41-55, 1972;.
37 +
Galin D:  Implications for psychiatry of left and right cerebral specialization . Arch Gen Psychiatry 31:572-583, 1974;.
38 +
Flor-Henry P:  Psychosis and temporal lobe epilepsy: A controlled investigation . Epilepsia 10:363-395, 1969;.
39 +
Bear DM, Fedio P:  Quantitative analysis of interictal behavior in temporal lobe epilepsy . Arch Neurol 34:454-467, 1977;.
40 +
LeDoux JE, Wilson DH, Gazzaniga MS:  A divided mind: Observations on the conscious properties of the separated hemispheres . Ann Neurol 2:417-421, 1977;.
41 +
Goodwin FK, Murphy DL, Dunner DL, et al:  Lithium response in unipolar versus bipolar depression . Am J Psychiatry 129:44-47, 1972;.
42 +
Prien RF, Klett CJ, Caffey EM Jr:  Lithium carbonate and imipramine in prevention of affective episodes . Arch Gen Psychiatry 29:420-425, 1973;.
43 +
Coppen AS, Montgomery SA, Gupta RK, et al:  A double-blind comparison of lithium carbonate and maprotiline in the prophylaxis of the affective disorders . Br J Psychiatry 128:479-485, 1976;.
44 +
Sheard MH, Aghajanian GK:  Neuronally activated metabolism of brain serotonin . Life Sci 9:285-290, 1970;.
45 +
Perez-Cruet J, Tagliamonte A, Tagliamonte P, et al:  Stimulation of brain serotonin turnover by lithium . Pharmacologist 12:257, 1970;.
46 +
Knapp S, Mandell AJ:  Short and long-term lithium administration: Effects on the brain's serotonergic biosynthetic systems . Science 180:645-647, 1973;.
47 +
Knapp S, Mandell AJ:  Effects of lithium chloride on parameters of biosynthetic capacity for 5-hydroxytryptamine in rat brain . J Pharmacol Exp Ther 193:812-823, 1975;.
48 +
Harding GFA, Lolas-Stepke F, Jenner FA:  Alpha rhythms, laterality, lithium and mood . Lancet 2:1248, 1976;.
49 +
Glick SD, Jerussi TP, Waters DH, et al:  Amphetamine-induced changes in striatal dopamine and acetylcholine levels and relationship to rotation (circling behavior) in rats . Biochem Pharmacol 23:3223-3225, 1974;.
50 +
Gerhart JC:  Subunits for control and catalysis in aspartate transcarbamylase . Brookhaven Symposium Subunit Structure of Proteins 17:222-231, 1964;.
51 +
Speijer N:  Treatment of a periodical psychosis (degenerative psychosis) based upon haematological and biochemical deviations from the normal . Folia Psychiatr Neurol Neurochir Neerl 53:718-726, 1950;.
52 +
Fischback R:  Changes in calcium metabolism in depression and during medication with thymoleptics . Arzneim Forsch 21:27-28, 1971;.
53 +
Carmen J, Post RM, Goodwin FK, et al:  Calcium and electroconvulsive therapy of severe depressive illness . Biol Psychiatry 12:5-7, 1977;.
54 +
Carman JS, Wyatt RJ:  Alterations in CSF and serum total calcium with changes in psychiatric state , in Usdin E, Hamburg DA, Barchas JD (eds): Neuroregulators and Psychiatric Disorders . New York, Oxford University Press Inc, 1977;, pp 488-494.
55 +
Carmen JS, Wyatt RJ: Calcium: Pace-setting the periodic psychoses. Read before the 131st annual meeting of the American Psychiatric Association, Atlanta, May 6, 1978.
56 +
Geyer MA, Puerto A, Dawsey WJ, et al:  Histologic and enzymatic studies of the mesolimbic and mesostriatal serotonergic pathways . Brain Res 106:241-256, 1976;.
57 +
Weinberger SB, Knapp S, Mandell AJ:  Failure of tryptophan loadinduced increases in brain serotonin to alter food intake in the rat . Life Sci 22:1595-1602, 1978;.
58 +
Geyer MA, Dawsey WJ, Mandell AJ:  Fading: A new cytofluorimetric measure quantifying serotonin in the presence of catecholamines at the cellular level in brain . J Pharmacol Exp Ther 207:650-667, 1978;.
59 +
Siegel S: Nonparametric Statistics . New York, McGraw-Hill, 1956;, p 271.
60 +
Knapp S, Mandell AJ:  Cocaine and lithium: Neurobiological antagonism in the serotonin biosynthetic system in rat brain . Life Sci 18:679-684, 1976;.
61 +
Ichiyama A, Nakamura S, Nishizuka Y, et al:  Enzymic studies on the biosynthesis of serotonin in mammalian brain . J Biol Chem 245:1699-1709, 1970;.
62 +
Mandell AJ, Knapp S:  Regulation of serotonin biosynthesis in brain: Role of the high affinity uptake of tryptophan into serotonergic neurons . Fed Proc 36:2142-2148, 1977;.
63 +
Friedman E, Gershon S, Rotrosen J:  Effects of acute cocaine treatment on the turnover of 5-hydroxytryptamine in the rat brain . Br J Pharmacol 54:61-64, 1975;.
64 +
Bullard WP, Guthrie PB, Russo PV, et al:  Regional and subcellular distribution and some factors in the regulation of reduced pterins in rat brain . J Pharmacol Exp Ther 206:4-20, 1978;.
65 +
Tagliamonte A, Tagliamonte S, Perez-Cruet J, et al:  Effect of psychotropic drugs on tryptophan concentration in the rat brain . J pharmacol Exp Ther 177:475-480, 1971;.
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Mandell AJ, Knapp S:  Neurobiological antagonism of cocaine by lithium , in Ellinwood EH (ed): Cocaine and Other Stimulants . New York, Plenum Press Inc, 1977;, pp 187-200.
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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Aghajanian GK, Wang RY:  Physiology and pharmacology of central serotonergic neurons , in Lipton MA, DiMascio A, Killam KF (eds): Psychopharmacology: A Generation of Progress . New York, Raven Press, 1978;, pp 171-184.
2 +
Davis M, Sheard MH:  Habituation and sensitization of the rat startle response: Effects of raphe lesions . Physiol Behav 12:425-431, 1974;.
3 +
Jouvet M:  Biogenic amines and the states of sleep . Science 163:32-39, 1969;.
4 +
Myers RD, Beleshin DB:  Changes in serotonin release in hypothalamus during cooling or warming of the monkey . Am J Physiol 220:1746-1753, 1971;.
5 +
Lints CE, Harvey JA:  Altered sensitivity to footshock and decreased brain content of serotonin following brain lesions in the rat . J Comp Physiol Psychol 67:23-31, 1969;.
6 +
Conner RL, Stolk JM, Barchas JD, et al:  The effect of p-chlorophenylalanine (PCPA) on shock-induced fighting behavior in rats . Physiol Behav 5:1221-1234, 1970;.
7 +
Fibiger HC, Campbell BA:  The effect of parachlorophenylalanine on spontaneous locomotor activity in the rat . Neuropharmacology 10:25-32, 1971;.
8 +
Wise CD, Berger BD, Stein L:  Serotonin: A possible mediator of behavioral suppression induced by anxiety . Dis Nerv Syst 31( (suppl) ):34-37, 1970;.
9 +
Meyerson BJ:  Central nervous monoamines and hormone induced estrus behavior in the spayed rat . Acta Physiol Scand 63( (suppl 241) ):1-32, 1964;.
10 +
Woolley DW:  A method for demonstration of the effects of serotonin on learning ability , in Mikhel'son M Ya, Lougo VG (eds): Pharmacology of Conditioning, Learning and Retention . Oxford, Pergamon Press, 1965;, pp 231-236.
11 +
Panksepp J, Nance DM:  Effects of para-chlorophenylalanine on food intake in rats . Physiol Psychol 2:360-364, 1974;.
12 +
Sailer CF, Stricker EM:  Hyperphagia and increased growth after intraventricular injection of 5,7-dihydroxytryptamine . Science 192:385-387, 1976;.
13 +
Geyer MA, Puerto A, Menkes DB, et al:  Behavioral studies following lesions of the mesolimbic and mesostriatal serotonergic pathways . Brain Res 106:257-270, 1976;.
14 +
Hollister AS, Breese GR, Kuhn CM, et al:  An inhibitory role for brain serotonin-containing systems in the locomotor effects of d-amphetamine . J Pharmacol Exp Ther 198:12-21, 1976;.
15 +
Isaacson RL, Wickelgren WO:  Hippocampal ablation and passive avoidance . Science 138:1104-1106, 1962;.
16 +
Essman WB:  Enhanced memory consolidation with drug-induced regional changes in brain RNA and serotonin metabolism . Pharmakopsychiatr Neuropsychopharmakol 2:28-34, 1969;.
17 +
Stein D, Jouvet M, Pujol JF:  Effects of a-methyl-p-tyrosine upon cerebral amine metabolism and sleep states in the cat . Brain Res 72:360-365, 1974;.
18 +
Hobson JA, McCarley RW, Wysinski PW:  Sleep cycle oscillation: Reciprocal discharge by two brain stem neuronal groups . Science 189:55-58, 1975;.
19 +
Fuxe K:  Evidence for the existence of monoamine neurons in the central nervous system: III. The monoamine nerve terminal . Z Zellforsch 65:572-596, 1965;.
20 +
Naumenko EV:  Hypothalamic chemoreactive structures and the regulation of pituitary-adrenal function . Brain Res 11:1-10, 1968;.
21 +
Bunney WE, Mason JW, Roatch JF:  A psychoendocrine study of severe psychotic depressive crisis . Am J Psychiatry 122:72-80, 1965;.
22 +
Van Praag HM:  Depressie en de stofunsseling van 5-hydroxytryptamine . Ned Tijdschr Geneeskd 113:2245-2247, 1969;.
23 +
Gershon ES, Targum SD, Kessler LR, et al:  Genetic studies and biological strategies in the affective disorders . Prog Med Genet 2:101-164, 1977;.
24 +
Azmitia EC, Buchan AM, Williams JH:  Structural and functional restoration by collateral sprouting of hippocampal 5-HT axons . Nature 274:374-376, 1978;.
25 +
Coppen A, Prange AJ Jr, Whybrow PC, et al:  Abnormalities of indoleamines in affective disorders . Arch Gen Psychiatry 26:474-478, 1972;.
26 +
Asberg M, Thoren P, Traskman L, et al:  Serotonin depression: A biochemical subgroup within the affective disorders . Science 191:478-480, 1976;.
27 +
Van Praag HM, Korf J, Schut D:  Cerebral monoamines and depression . Arch Gen Psychiatry 28:827-831, 1973;.
28 +
Goodwin FK, Extein IL, Wehr TA:  Some recent advances in psychobiology and psychopharmacology of affective disorders , in Ayd FJ, Taylor IJ (eds): Mood Disorders: The World's Major Public Health Problem . Baltimore, Ayd Medical Communications, 1978;, pp 22-43.
29 +
Harnad S, Doty RW, Goldstein L, et al (eds): Lateralization in the Nervous System . New York, Academic Press Inc, 1977;.
30 +
Mandell AJ, Knapp S:  Regulatory properties of tryptophan hydroxylase determine the degree of bilateral asymmetry in mesolimbic serotonin synthesis: A model for mood control . Fed Proc , to be published.
31 +
Mandell AJ:  Toward a psychobiology of transcendence: God in the brain , in Davidson JM, Davidson RJ (eds): The Psychobiology of Consciousness . New York, Plenum Press Inc, to be published.
32 +
Mandell AJ, Knapp S, Geyer MA:  Lithium decreases and cocaine increases the bilateral asymmetry of serotonin in mesostriatal and mesolimbic systems associated with changes in the kinetic properties of tryptophan hydroxylase , in Usdin E (ed): Catecholamines: Basic and Clinical Frontiers . New York, Pergamon Press, to be published.
33 +
Knapp S, Mandell AJ:  Conformational influences on brain tryptophan hydroxylase activity by submicromolar calcium: opposite effects of equimolar lithium . J Neural Transm , to be published.
34 +
Weinstein EA, Kahn RC: Denial of Illness: Symbolic and Physiological Aspects . Springfield, Ill, Charles C Thomas Publisher, 1955;.
35 +
Terzian H:  Behavioral and EEG effects of intracarotid sodium amytal injections . Acta Neurochir 12:230-240, 1964;.
36 +
Gainotti G:  Emotional behavior and hemispheric side of the lesion . Cortex 8:41-55, 1972;.
37 +
Galin D:  Implications for psychiatry of left and right cerebral specialization . Arch Gen Psychiatry 31:572-583, 1974;.
38 +
Flor-Henry P:  Psychosis and temporal lobe epilepsy: A controlled investigation . Epilepsia 10:363-395, 1969;.
39 +
Bear DM, Fedio P:  Quantitative analysis of interictal behavior in temporal lobe epilepsy . Arch Neurol 34:454-467, 1977;.
40 +
LeDoux JE, Wilson DH, Gazzaniga MS:  A divided mind: Observations on the conscious properties of the separated hemispheres . Ann Neurol 2:417-421, 1977;.
41 +
Goodwin FK, Murphy DL, Dunner DL, et al:  Lithium response in unipolar versus bipolar depression . Am J Psychiatry 129:44-47, 1972;.
42 +
Prien RF, Klett CJ, Caffey EM Jr:  Lithium carbonate and imipramine in prevention of affective episodes . Arch Gen Psychiatry 29:420-425, 1973;.
43 +
Coppen AS, Montgomery SA, Gupta RK, et al:  A double-blind comparison of lithium carbonate and maprotiline in the prophylaxis of the affective disorders . Br J Psychiatry 128:479-485, 1976;.
44 +
Sheard MH, Aghajanian GK:  Neuronally activated metabolism of brain serotonin . Life Sci 9:285-290, 1970;.
45 +
Perez-Cruet J, Tagliamonte A, Tagliamonte P, et al:  Stimulation of brain serotonin turnover by lithium . Pharmacologist 12:257, 1970;.
46 +
Knapp S, Mandell AJ:  Short and long-term lithium administration: Effects on the brain's serotonergic biosynthetic systems . Science 180:645-647, 1973;.
47 +
Knapp S, Mandell AJ:  Effects of lithium chloride on parameters of biosynthetic capacity for 5-hydroxytryptamine in rat brain . J Pharmacol Exp Ther 193:812-823, 1975;.
48 +
Harding GFA, Lolas-Stepke F, Jenner FA:  Alpha rhythms, laterality, lithium and mood . Lancet 2:1248, 1976;.
49 +
Glick SD, Jerussi TP, Waters DH, et al:  Amphetamine-induced changes in striatal dopamine and acetylcholine levels and relationship to rotation (circling behavior) in rats . Biochem Pharmacol 23:3223-3225, 1974;.
50 +
Gerhart JC:  Subunits for control and catalysis in aspartate transcarbamylase . Brookhaven Symposium Subunit Structure of Proteins 17:222-231, 1964;.
51 +
Speijer N:  Treatment of a periodical psychosis (degenerative psychosis) based upon haematological and biochemical deviations from the normal . Folia Psychiatr Neurol Neurochir Neerl 53:718-726, 1950;.
52 +
Fischback R:  Changes in calcium metabolism in depression and during medication with thymoleptics . Arzneim Forsch 21:27-28, 1971;.
53 +
Carmen J, Post RM, Goodwin FK, et al:  Calcium and electroconvulsive therapy of severe depressive illness . Biol Psychiatry 12:5-7, 1977;.
54 +
Carman JS, Wyatt RJ:  Alterations in CSF and serum total calcium with changes in psychiatric state , in Usdin E, Hamburg DA, Barchas JD (eds): Neuroregulators and Psychiatric Disorders . New York, Oxford University Press Inc, 1977;, pp 488-494.
55 +
Carmen JS, Wyatt RJ: Calcium: Pace-setting the periodic psychoses. Read before the 131st annual meeting of the American Psychiatric Association, Atlanta, May 6, 1978.
56 +
Geyer MA, Puerto A, Dawsey WJ, et al:  Histologic and enzymatic studies of the mesolimbic and mesostriatal serotonergic pathways . Brain Res 106:241-256, 1976;.
57 +
Weinberger SB, Knapp S, Mandell AJ:  Failure of tryptophan loadinduced increases in brain serotonin to alter food intake in the rat . Life Sci 22:1595-1602, 1978;.
58 +
Geyer MA, Dawsey WJ, Mandell AJ:  Fading: A new cytofluorimetric measure quantifying serotonin in the presence of catecholamines at the cellular level in brain . J Pharmacol Exp Ther 207:650-667, 1978;.
59 +
Siegel S: Nonparametric Statistics . New York, McGraw-Hill, 1956;, p 271.
60 +
Knapp S, Mandell AJ:  Cocaine and lithium: Neurobiological antagonism in the serotonin biosynthetic system in rat brain . Life Sci 18:679-684, 1976;.
61 +
Ichiyama A, Nakamura S, Nishizuka Y, et al:  Enzymic studies on the biosynthesis of serotonin in mammalian brain . J Biol Chem 245:1699-1709, 1970;.
62 +
Mandell AJ, Knapp S:  Regulation of serotonin biosynthesis in brain: Role of the high affinity uptake of tryptophan into serotonergic neurons . Fed Proc 36:2142-2148, 1977;.
63 +
Friedman E, Gershon S, Rotrosen J:  Effects of acute cocaine treatment on the turnover of 5-hydroxytryptamine in the rat brain . Br J Pharmacol 54:61-64, 1975;.
64 +
Bullard WP, Guthrie PB, Russo PV, et al:  Regional and subcellular distribution and some factors in the regulation of reduced pterins in rat brain . J Pharmacol Exp Ther 206:4-20, 1978;.
65 +
Tagliamonte A, Tagliamonte S, Perez-Cruet J, et al:  Effect of psychotropic drugs on tryptophan concentration in the rat brain . J pharmacol Exp Ther 177:475-480, 1971;.
66 +
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Compression-Only CPR: Pushing the Science Forward
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BMJ 2010;341:c5893-c1494.
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