Article| Volume 27, ISSUE 10, P1143-1155, May 15, 1990

Download started.


Effects of age and gender on CNS serotonergic responsivity in normal adults

      This paper is only available as a PDF. To read, Please Download here.


      The effects of age and genderon central nervous system (CNS) serotonergic responsivity were asseseed with a neuroendocrine challenge test in 30 normal adults. Subjects ⩾30 years of age, compared with younger subjects, exhibited decreased prolactin secretion in response to a 60-mg oral dose of dl-fendluramine hydrochloride, an indirect serotonin agonist. Furthermore, women had greater prolactin responses than men. As prolactin secretory capacity appears to be stable through midlife, the age-associated decrease in fenfluramine-induced prolactin release suggests a decline in CNS serotonergic In contrast, the finding of greater prolactin release in women than in men probably reflects the effects of nonserotonergic modulatory influences at the level of the lactotroph. Age and gender effects must be considered in studies of the CNS serotonergic system.


        • Allen S.J.
        • Benton J.S.
        • Goodhardt M.J.
        • et al.
        Biochemical evidence of selective nerve cell changes in the normal ageing human and rat brain.
        J Neurochem. 1983; 41: 256-265
        • Anderson G.M.
        Monoamines in autism: An update of neurochemical research on a pervasive developmental disorder.
        Med Biol. 1987; 65: 67-74
        • Asberg M.
        • Bertilsson L.
        • Tuck D.
        • Cronholm B.
        • Sjoquist F.
        Indoleamine metabolites in the cerebrospinal fluid of depressed patients before and during treatment with nortriptyline.
        Clin Pharmacol Ther. 1973; 14: 277-286
        • Asnis G.
        • Eisenberg J.
        • van Praag H.M.
        • Lemus C.Z.
        • Harkavy Friedman J.M.
        • Miller A.H.
        The neuroendocrine response to fenfluramine in depressives and normal controls.
        Biol Psychiatry. 1988; 24: 117-120
        • Baskys A.
        • Niesen C.E.
        • Carlen P.L.
        Altered modulatory actions of serotonin on dentate granule cells of aged rats.
        Brain Res. 1987; 419: 112-118
        • Ben-Jonathan N.
        Dopamine: A prolactin-inhibiting hormone.
        Endocrinol Rev. 1985; 6: 564-589
        • Bennett J.P.
        • Enna S.J.
        • Bylund D.B.
        • Gillin J.C.
        • Wyatt R.J.
        • Snyder S.H.
        Neurotransmitter receptors in frontal cortex of schizophrenics.
        Arch Gen Psychiatry. 1979; 36: 927-934
        • Borroni E.
        • Ceci A.
        • Garattini S.
        • Mennini T.
        Differences between D-fenfluramine and D-norfenfluramine in serotonin presynaptic mechanisms.
        J Neurochem. 1983; 40: 891-893
        • Bucht G.
        • Adolfsson R.
        • Gottfries C.G.
        • Roos B.-E.
        • Winblad B.
        Distribution of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in human brain in relation to age, drug influence, agonal status and circadian variation.
        J Neural Transm. 1981; 51: 185-203
        • Burrow G.N.
        • May P.B.
        • Spaulding S.W.
        • Donabedian R.K.
        TRH and dopamine interactions affecting pituitary hormone secretion.
        J Clin Endocrinol Metab. 1977; 45: 65-72
        • Carlson H.E.
        Carbidopa plus L-dopa pretreatment inhibits the prolactin (PRL) response to thyrotropin-releasing hormone and thus cannot distinguish central from pituitary sites of prolactin stimulation.
        J Clin Endocrinol Metab. 1986; 63: 249-251
        • Carlsson A.
        Neurotransmitter changes in the aging brain.
        Dan Med Bull. 1985; 32 (Suppl): 40-43
        • Carlsson A.
        • Adolfsson R.
        • Aquilonius S.M.
        • et al.
        Biogenic amines in human brain in normal aging, senile dementia, and chronic alcoholism.
        in: Goldstein M. Ergot Compounds and Brain Function: Neuroendocrine and Neuropsychiatric Aspects. Raven Press, New York1980: 295-304
        • Carlsson M.
        • Svensson K.
        • Eriksson E.
        • Carlsson A.
        Rat brain serotonin: Biochemical and functional evidence for a sex difference.
        J Neurol Transm. 1985; 63: 297-313
        • Charney D.S.
        • Goodman W.K.
        • Price L.H.
        • Woods S.W.
        • Rasmussen S.A.
        • Heninger G.R.
        Serotonin function in obsessive-compulsive disorder: A comparison of the effects of tryptophan and m-chlorophenylpiperazine in patients and healthy subjects.
        Arch Gen Psychiatry. 1988; 45: 177-185
        • Coccaro E.F.
        • Siever L.J.
        • Klar H.M.
        • et al.
        Serotonergic studies in patients with affective and personality disorders: Correlates with suicidal and impulsive aggressive behavior.
        Arch Gen Psychiatry. 1989; 46: 587-599
        • Fischette C.T.
        • Biegon A.
        • McEwen B.S.
        Sex steroid modulation of the serotonin behavioral syndrome.
        Life Sci. 1984; 35: 1997-2006
        • Fowler C.J.
        • Tipton K.F.
        On the substrate specificities of two forms of monoamine oxidase.
        J Pharm Pharmacol. 1984; 36: 111-115
        • Fowler C.J.
        • Wiberg A.
        • Oreland L.
        • Marcusson J.
        • Winblad B.
        The effect of age on the activity and molecular properties of human brain monoamine oxidase.
        J Neural Transm. 1980; 49: 1-20
        • Fuller R.W.
        • Snoddy H.D.
        • Clemens J.A.
        • Molloy B.B.
        Effect of norfenfluramine and two structural analogues on brain 5-hydroxyindoles and serum prolactin in rats.
        J Pharm Pharmacol. 1982; 34: 449-450
        • Heninger G.R.
        • Charney D.S.
        • Sternberg D.E.
        Serotonergic function in depression: Prolactin response to intravenous tryptophan in depressed patients and healthy subjects.
        Arch Gen Psychiatry. 1984; 41: 398-402
        • Insel T.R.
        • Mueller E.A.
        • Alterman I.
        • Linnoila M.
        • Murphy D.L.
        Obssssive-compulsive disorder and serotonin: Is there a connection?.
        Biol Psychiatry. 1985; 20: 1174-1188
        • Jacobs L.S.
        • Snyder P.J.
        • Utiger R.D.
        • Daughaday W.H.
        Prolactin response to thyrotropin-releasing hormone in normal subjects.
        J Clin Endocrinol Metab. 1973; 36: 1069-1073
        • Jacques C.
        • Cchlienger J.L.
        • Kissel C.
        • Kuntzmann C.
        • Sapin R.
        TRH-induced TSH and prolactin responses in the elderly.
        Age Ageing. 1987; 16: 181-188
        • Kato Y.
        • Matsushita N.
        • Ohta H.
        • Tojo H.
        • Shimatsu A.
        • Imura H.
        Regulation of prolactin secretion.
        in: Imura H. The Pituitary Gland. Raven Press, New York1985: 261-278
        • Krebs H.A.
        • Cheng L.K.
        • Wright G.J.
        Determination of fenfluramine and norfenfluramine in plasma using a nitrogen-sensitive detector.
        J Chromatogr. 1984; 310: 412-417
        • Levitt P.
        • Pintar J.E.
        • Breakefield X.O.
        Immunocytochemical demonstration of monoamine oxidase B in brain astrocytes and serotonergic neurons.
        in: Proc Natl Acad Sci USA. 79. 1982: 6385-6389
        • MacLeod R.M.
        • Login I.S.
        Regulation of prolactin secretion through dopamine, serotonin and the cerebrospinal fluid.
        Adv Biochem Psychopharmacol. 1977; 16: 147-157
        • Mann J.J.
        • Petito C.
        • Stanley M.
        • McBride P.A.
        • Chin J.
        • Philogene A.
        Amine receptor binding and monoamine oxidase activity in postmortem human brain tissue: Effect of age, gender, and postmortem delay.
        in: Burrows G.D. Norman T.R. Dennerstein L. Clinical and Pharmacologic Studies in Psychiatric Disorders. John Libbey & Co, London1985: 37-39
        • Mann J.J.
        • Stanley M.
        Postmortem monoamine oxidase enzyme kinetics in the frontal cortex of suicide victims and controls.
        Acta Psychiatr Scand. 1984; 69: 135-139
        • Mann J.J.
        • Stanley M.
        • McBride P.A.
        • McEwen B.S.
        Increased serotonin and B-adrenergic receptor binding in the frontal cortices of suicide victims.
        Arch Gen Psychiatry. 1986; 43: 954-959
        • Marcusson J.O.
        • Oreland L.
        • Winblad B.
        Effect of age on human brain serotonin (S-1) binding sites.
        J Neurochem. 1984; 43: 1699-1705
        • Marcusson J.O.
        • Morgan D.G.
        • Winblad B.
        • Finch G.E.
        Serotonin-2 binding sites in human frontal cortex and hippocampus: Selective loss of S-2A sites with age.
        Brain Res. 1984; 311: 51-56
        • Martinez de la Escalera G.
        • Weiner R.I.
        mechanism(s) by which the transient removal of dopamine regulation potentiates the prolactin-releasing action of thyrotropin-releasing hormone.
        Neuroendocrinology. 1988; 47: 186-193
        • McBride P.A.
        • Anderson G.M.
        • Hertzig M.E.
        • et al.
        Serotonergic responsibity in male young adults with autistic disorder: Results of a pilot study.
        Arch Gen Psychiatry. 1989; 46: 213-221
        • McBride P.A.
        • Kream J.
        • Anderson G.
        • Mann J.J.
        Effect of age upon measures of central and peripheral serotonergic function in human subjects (Abstract).
        in: Society for Neuroscience Annual Meeting. 1986: 1313
        • Meites J.
        • Goya R.
        • Takahashi S.
        Why the neuroendcrine system is important in aging processes.
        Exp Gerentol. 1987; 22: 1-15
        • Meltzer H.Y.
        • Wiita B.
        • Tricou B.J.
        • Simonovic M.
        • Fang V.
        • Manov G.
        Effect of serotonin precursors and serotonin agonists on plasma hormone levels.
        in: Ho B.T. Schoolar J.C. Usdin E. Serotonin in Biological Psychiatry. Raven Press, New York1982: 117-139
        • Morgan D.G.
        • May P.C.
        • Finch C.E.
        Dopamine and serotonin systems in human and rodent brain: Effects of age and neurodegenerative disease.
        J Am Geriatr Soc. 1987; 35: 334-345
        • Mueller E.A.
        • Murphy D.L.
        • Sunderland T.
        Neuroendocrine effects of M-chlorophenylpiperazine, a serotonin agonist, in humans.
        J Clin Endocrinol Metab. 1985; 61: 1179-1184
        • Munaro N.I.
        The effect of ovarian steroids on hypothalamic 5-hydroxytryptamine neuronal activity.
        Neuroendocrinology. 1978; 26: 270-276
        • Quattrone A.
        • Di Renzo G.F.
        • Schettini G.
        • Tedeschi G.
        • Scopacasa F.
        Increased plasma prolactin levels induced in rats by d-fenfluraine: Relation to central serotonergic stimulation.
        Eur J Pharmacol. 1978; 49: 163-167
        • Quattrone A.
        • Tedeschi G.
        • Aguglia U.
        • Scopacasa F.
        • Di Renzo G.F.
        • Annunziato L
        Prolactin secretion in man, a useful tool to evaluate the activity of drugs on central 5-hydroxytryptaminergic neurons: Studies with fenfluramine.
        Br J Pharmaol. 1983; 16: 471-475
        • Segal M.
        Changes in neurotransmitter actions in the aged rat hippocampus.
        Neurobiol Aging. 1982; 3: 121-124
        • Severson J.A.
        • Marcusson J.O.
        • Osterburg H.H.
        • Finch C.E.
        • Winblad B.
        Elevated density of [3H]imipramine binding in aged human brain.
        J Neurochem. 1985; 45: 1382-1389
        • Stanley M.
        • Virgilio J.
        • Gershon S.
        Tritiated imipramine binding sites are decreased in the frontal cortex of suicides.
        Science. 1982; 216: 1337-1339
        • van Praag H.M.
        Indoleamines in depression and suicide.
        Prog Brain Res. 1986; 65: 59-71
        • von Knorring L.
        • Oreland L.
        • Haggendal J.
        • Magnusson T.
        • Almay B.
        • Johansson F.
        Relationship between plateet MAO activity and concentrations of 5-HIAA and HVA in cerebrospinal fluid in chronic pain patients.
        J Neural Transm. 1986; 66: 37-46
        • Wester P.
        • Hardy J.A.
        • Marcusson J.
        • et al.
        Serotonin concentrations in normal aging human brains: Relation to serotonin receptors.
        Neurobiol Aging. 1984; 5: 199-203
        • Wong D.F.
        • Wagner H.N.
        • Dannals R.F.
        • et al.
        Effects of age on dopamine and serotonin receptors measured by position tomography in the living human brain.
        Science. 1984; 226: 1393-1396