Pharmacopsychiatry 2010; 43(7): 277-278
DOI: 10.1055/s-0030-1263175
Letter

© Georg Thieme Verlag KG Stuttgart · New York

Nocturnal Administration of Ghrelin does not Promote Memory Consolidation

M. Dresler1 , M. Kluge1 , 2 , L. Genzel1 , P. Schüssler1 , A. Steiger1
  • 1Endocrinology of Sleep, Max Planck Institute of Psychiatry, Munich, Germany
  • 2Present address: Department of Psychiatry, University of Leipzig, Leipzig, Germany
Further Information

Publication History

received 15.03.2010 revised 07.07.2010

accepted 21.07.2010

Publication Date:
14 September 2010 (online)

Introduction

Ghrelin is an endogenous ligand of the growth hormone secretagogue receptor produced peripherally and centrally. A growing number of studies in mice and rats shows that administration of ghrelin improves several memory processes [3] [4] [5] [7]. However, also an impairment of memory retention in neonatal chicks after ghrelin administration has been reported [6]. In their recent paper, Atcha and colleagues [2] report that ghrelin receptor agonists enhance memory retention in rats. In line with other authors (e. g., [18]), they propose the central ghrelin receptor as a new drug target for therapeutic approaches to treat diseases affecting cognition.

Administration of ghrelin also interacts with sleep regulation. While ghrelin promotes non-rapid eye movement sleep in human males [11] [12] [21] and in mice [13], it suppresses sleep in rats [16] [17]. Sleep, on the other hand, has been shown to enhance nocturnal plasma ghrelin levels [10] and to play a crucial role in memory consolidation [15]. It is discussed to what extent several hormones might play a key role in this process [19]. Especially off-line gains in newly acquired sequential motor skills seem to be exclusively bound to sleep [15], a process in which the hippocampus has been shown to be involved [1]. Despite these reciprocal interactions between memory, ghrelin and sleep, no studies about the effects of ghrelin administration on sleep-associated memory consolidation exist so far. We therefore studied if nocturnal pulsatile ghrelin administration influences the consolidation of a motor learning task in humans.

References

  • 1 Albouy G, Sterpenich V, Balteau E. et al . Both the hippocampus and striatum are involved in consolidation of motor sequence memory.  Neuron. 208;  58 261-272
  • 2 Atcha Z, Chen WS, Ong AB. et al . Cognitive enhancing effects of ghrelin receptor agonists.  Psychopharmacology. 2009;  206 415-427
  • 3 Carlini VP, Monzon ME, Varas MM. et al . Ghrelin increases anxiety-like behavior and memory retention in rats.  Biochem Biophys Res Commun. 2002;  299 739-743
  • 4 Carlini VP, Varas MM, Cragnolini AB. et al . Differential role of the hippocampus, amygdala, and dorsal raphe nucleus in regulating feeding, memory, and anxiety-like behavioral responses to ghrelin.  Biochem Biophys Res Commun. 2004;  313 635-641
  • 5 Carlini VP, Martini AC, Schioth HB. et al . Decreased memory for novel object recognition in chronically food-restricted mice is reversed by acute ghrelin administration.  Neuroscience. 2008;  153 929-934
  • 6 Carvajal P, Carlini VP, Schiöth HB. et al . Central ghrelin increases anxiety in the Open Field test and impairs retention memory in a passive avoidance task in neonatal chicks.  Neurobiol Learn Mem. 2009;  91 402-407
  • 7 Diano S, Farr SA, Benoit SC. et al . Ghrelin controls hippocampal spine synapse density and memory performance.  Nat Neurosci. 2006;  9 381-388
  • 8 Dresler M, Kluge M, Genzel L. et al . Impaired off-line memory consolidation in depression.  European Neuropsychopharmacology. 2010;  20 553-561
  • 9 Dresler M, Genzel L, Kluge M. et al . Off-line memory consolidation impairments in multiple sclerosis patients receiving high-dose corticosteroid treatment mirror consolidation impairments in depression.  Psychoneuroendocrinology. 2010;  in press
  • 10 Dzaja A, Dalal MA, Himmerich H. et al . Sleep enhances plasma ghrelin levels in healthy subjects.  Am J Physiol Endocrinol Metab. 2004;  286 E963-E967
  • 11 Kluge M, Schüssler P, Bleninger P. et al . Ghrelin alone or co-administered with GHRH or CRH increases non-REM sleep and decreases REM sleep in young males.  Psychoneuroendocrinology. 2008;  33 497-506
  • 12 Kluge M, Uhr M, Bleninger P. et al . Ghrelin suppresses secretion of follicle stimulating hormone (FSH) in males.  Clin Endocrinol (Oxf). 2009;  70 920-923
  • 13 Obal Jr F, Alt J, Taishi P. et al . Sleep in mice with nonfunctional growth hormone-releasing hormone receptors.  Am J Physiol Regul Integr Comp Physiol. 2003;  284 R131-R139
  • 14 Rechtschaffen A, Kales A. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects.. Bethesda, MD: US Department of Health, Education and Welfare, Public Health Services; 1968
  • 15 Stickgold R. Sleep-dependent memory consolidation.  Nature. 437;  2005 1272-1278
  • 16 Szentirmai E, Hajdu I, Obál Jr F. et al . Ghrelin-induced sleep responses in ad libitum fed and food-restricted rats.  Brain Res. 2006;  1088 131-140
  • 17 Szentirmai É, Kapás L, Krueger JM. Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats.  Am J Physiol Regul Integr Comp Physiol. 2007;  292 R575-R585
  • 18 Thomas L. An appetite for learning.  Lancet Neurology. 2006;  5 299
  • 19 Wagner U, Born J. Memory consolidation during sleep: Interactive effects of sleep stages and HPA regulation.  Stress. 2008;  11 28-41
  • 20 Walker M P, Brakefield T, Morgan A. et al . Practice with sleep makes perfect: Sleep-dependent motor skill learning.  Neuron. 2002;  35 205-211
  • 21 Weikel JC, Wichniak A, Ising M. et al . Ghrelin promotes slow-wave sleep in humans.  Am J Physiol Endocrinol Metab. 2003;  284 E407-E415

Correspondence

M. Dresler

Max Planck Institute of Psychiatry

Kraepelinstraße 2–10

80804 Munich

Germany

Phone: +49/89/30622 386

Fax: +49/89/30622 552

Email: dresler@mpipsykl.mpg.de

    >