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01-09-2006 | Original Paper

Psychopharmacology of maternal separation anxiety in vervet monkeys

Authors: Lelanie Marais, Willie Daniels, Linda Brand, Francois Viljoen, Charmaine Hugo, Dan J. Stein

Published in: Metabolic Brain Disease | Issue 2-3/2006

Abstract

Maternal separation in non-human primates has been proposed as a model of early adversity. The symptoms of separation anxiety were studied in vervet monkeys, during the weaning period, when psychotropic medications were administered. The control group received a normal diet and treatment groups received citalopram, reboxetine or lamotrigine in their food daily. Treatment was given for 7 weeks starting 1 month prior to weaning. Behavior was recorded twice weekly for 8 weeks, and was rated for anxiety and depression. Cerebrospinal fluid was collected at the beginning and end of the trial and analyzed for monoamines and metabolites using High Performance Liquid Chromatography. Citalopram pretreatment prevented the reduction of affiliation behavior and reduced stereotypies after weaning, and both citalopram and reboxetine abolished the increase in activity seen in control monkeys after weaning, but no statistically significant differences were found between groups. Citalopram pretreatment also significantly increased noradrenaline and 5-hydroxyindolacetic acid (5-HIAA) levels and reboxetine significantly decreased dopamine levels over time. The 5-HIAA levels of reboxetine and lamotrigine treated monkeys were significantly lower than that of the control group at the end of the trial. Although limited by a small sample size, this study demonstrates the possibility of investigating the psychopharmacology of early adversity in a non-human primate model.

Anderson GM, Bennett AJ, Weld KP, Pushkas JG, Ocarne DM, Higley JD (2002) Serotonin in cerebrospinal fluid of rhesus monkeys: basal levels and effects of sertraline administration. Psychopharmacology 161:95–99PubMedCrossRef

Carpenter LL, Anderson GM, Siniscalchi JM, Chappell PB, Price LH (2003) Acute changes in cerebrospinal fluid 5-HIAA following oral paroxetine challenge in healthy humans. Neuropsychopharmacology 28:339–347PubMedCrossRef

Charney DS, Drystal JJ, Southwick SM, Nagy LM, Woods SW, Heninger GR (1990) Serotonin function in panic and generalized anxiety disorders. Psychiatr Ann 20:593–604

David DJP, Bourin M, Jego G, Przybylski C, Jolliet P, Gardier AM (2003) Effects of acute treatment with paroxetine, citalopram and venlafaxine in vivo on noradrenaline and serotonin outflow: a microdialysis study in Swiss mice. Br J Pharmacol 140:1128–1136PubMedCrossRef

Gorman JM, Mathew S, Coplan J (2002) Neurobiology of early life stress: nonhuman primate models. Semin Clin Neuropsychiatry 7:96–103PubMedCrossRef

Harvey BH, Brand L, Jeeva Z, Stein DJ (2006) Cortical/hippocampal monoamines, HPA-axis changes and aversive behavior following stress and re-stress in an animal model of post traumatic stress disorder. Physiology and Behavior (in press)

Hinde RA, Spencer-Booth Y (1971) Effects of brief separation from mother on rhesus monkeys. Science 173:111–118PubMedCrossRef

Hughes ZA, Stanford SC (1998) Evidence from microdialysis and synaptosomal studies of rat cortex for noradrenaline uptake sites with different sensitivities to SSRIs. Br J Pharmacol 124:1141–1148PubMedCrossRef

Hugo C, Seier J, Mdhluli C, Daniels W, Harvey B, Du Toit D, Wolfe-Coote S, Nel D, Stein D (2003) Fluoxetine decreases stereotypic behaviour in primates. Prog Neuropsychopharmacol Biol Psychiatry 27:639–643PubMedCrossRef

Hugo CJ, Seier J, Mdhluli C, van Niekerk C, Daniels W, du Toit DF, Wolfe-Coote S, Stein DJ (2001) Use of fluoxetine for separation anxiety in primates. Paper presented at the Psychopharmacology Congress, Stellenbosch, South Africa

Insel TR (1990) Serotonin in obsessive-compulsive disorder. Psychiatr Ann 20:558–559

Kalin NH, Shelton SE, Barksdale CM (1988) Opiate modulation of separation-induced distress in non-human primates. Brain Res 440:285–292PubMedCrossRef

Kraemer GW, Ebert MH, Schmidt DE, McKinney WT (1991) Strangers in a strange land: a psychobiological study of infant monkeys before and after separation from real or inanimate mothers. Child Dev 62:548–566PubMedCrossRef

Kraemer GW, Ebert MH, Schmidt DE, McKinney WT (1989) A longitudinal study of the effect of different social rearing conditions on cerebrospinal fluid norepinephrine and biogenic amine metabolites in rhesus monkeys. Neuropsychopharmacology 2:175–189PubMedCrossRef

Koch S, Perry KW, Nelson DL, Conway RG, Threlkeld PG, Bymaster FP (2002) R-fluoxetine increases extracellular DA, NE, as well as 5-HT in rat prefrontal cortex and hypothalamus: an in vivo microdialysis and receptor binding study. Neuropsychopharmacol 27:949–959CrossRef

Laudenslager ML, Held PE, Boccia ML, Cohen JJ (1990) Behavioural and immunology consequences of brief maternal separation: a species comparison. Dev Psychobiol 23:247–264PubMedCrossRef

Leger L, Descarries L (1978) Serotonin nerve terminals in the locus coeruleus of adult rat: a radioautographic study. Brain Res 145:1–13PubMedCrossRef

Luckett WP, Szalay FS (1975) Phylogeny of the Primates. Plenum Press, New York and London

Maj J, Dziedzicka-Wasylewska M, Rogoz R, Rogoz Z (1998) Effect of antidepressant drugs administered repeatedly on the dopamine D₃ receptors in the rat brain. Eur J Pharmacol 351:31–37PubMedCrossRef

Maj J, Dziedzicka-Wasylewska M, Rogoz R, Rogoz Z, Skuza G (1996) Antidepressant drugs given repeatedly change the binding of dopamine D₂ receptor agonist, [³H]N-0437, to dopamine D₂ receptors in the rat brain. Eur J Pharmacol 304:49–54PubMedCrossRef

Meltzer HY, Lowy MT (1987) The serotonin hypotheses of depression. In: Meltzer HY (ed) Psychopharmacology: The Third Generation of Progress. Raven Press, New York, pp. 513–526

Meyer JS, Novak MA, Bowman RE, Harlow HF (1975) Behavioral and hormonal effects of attachment object separation in surrogate-peer-reared and mother-reared infant rhesus monkeys. Dev Psychobiol 8:425–435PubMedCrossRef

Millan MJ, Dekeyne A, Gobert A (1998) Serotonin (5-HT)2C receptors tonically inhibit dopamine (DA) and noradrenaline (NA), but not 5-HT, release in the frontal cortex in vivo. Neuropharmacol 37:953–955CrossRef

Morgane JP, Jacobs MS (1979) Raphe projections to the locus coeruleus in the rat. Brain Res Bull 4:519–534PubMedCrossRef

Owens MJ, Knight DL, Nemeroff CB (2001) Second-generation SSRIs: human monoamine transporter binding profile of Escitalopram and R-flouxetine. Biol Psychiatr 50:345–350CrossRef

Pickel VM, Joh TH, Reis DJ (1977) A serotonergic innervation of noradrenergic neurons in nucleus locus coeruleus: demonstration by immunocytochemical localization of the transmitter specific enzymes tyrosine and tryptophan hydroxylase. Brain Res 131:197–214PubMedCrossRef

Rogoz Z, Margas W, Skuza G, Solich J, Kusmider M, Dziedzicka-Wasylewska M (2002) Effect of repeated treatment with reboxetine on the central α₁-adrenergic and dopaminergic receptors. Pol J Pharmacol 54:593–603PubMed

Rosenblum LA, Andrews MW (1994) Influences of environmental demand on maternal behavior and infant development. Acta Paediatr Suppl 397:57–63PubMedCrossRef

Sanchez MM, Ladd CO, Plotsky PM (2001) Early adverse experience as a developmental risk factor for later psychopathology: evidence from rodent and primate models. Dev Psychopathol 13:419–449PubMedCrossRef

Smith TD, Kuczenski R, George-Friedman K, Malley JD, Foote SL (2000) In vivo microdialysis assessment of extracellular serotonin and dopamine levels in awake monkeys during sustained fluoxetine administration. Synapse 38:460–470PubMedCrossRef

Sulser F (1984) Antidepressant treatments and regulation of norepenephrine-receptor-coupled adenylate cyclase systems in brain. In: Usdin E (ed) Frontiers in Biochemical and Pharmacological Research in Depression. Raven Press, New York, pp. 249–261

Sulser F (1989) New perspectives on the molecular pharmacology of affective disorder. Eur Arch Psychiatry Neurol Sci 238:231–239PubMedCrossRef

Zohar J, Insel TR (1987) Obsessive-compulsive disorder: psychobiological approaches to diagnosis, treatment, and pathophysiology. Biol Psychiatry 22:667–87PubMedCrossRef

Title: Psychopharmacology of maternal separation anxiety in vervet monkeys
Authors: Lelanie Marais
Willie Daniels
Linda Brand
Francois Viljoen
Charmaine Hugo
Dan J. Stein
Publication date: 01-09-2006
Publisher: Kluwer Academic Publishers-Plenum Publishers
Published in: Metabolic Brain Disease / Issue 2-3/2006
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-006-9011-8

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Psychopharmacology of maternal separation anxiety in vervet monkeys

Abstract

Keynote webinar | Spotlight on medication adherence

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Abstract

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