ReviewListening to neuropeptides by microdialysis: Echoes and new sounds?Carsten T. Wotjaka,?, Rainer Landgrafa, Mario EngelmannbaMax-Planck-Institut für Psychiatrie, Kraepelinstr. 2, D-80804 München, GermanybOtto-von-Guericke-Universität Magdeburg, Institut für Medizinische Neurobiologie, Leipziger Str. 44, D-39120 Magdeburg, GermanyA B S T R A C TA R T I C L EI N F OArticle history:Received 18 December 2007Received in revised form 10 March 2008Accepted 24 March 2008Available online 1 April 2008Keywords:Push–pull perfusionVasopressinOxytocinMicrodialysisNeuropeptides represent the largest class of neuromessengers in the central nervous system. They areinvolved in the regulation of growth processes, reproduction, social behavior, emotion/motivation andcognition. Particularly in subcortical structures, neuropeptides act as neuromodulators, which reach theirtarget sites via diffusion through the extracellular space. This route of information transfer together with theability of neurons to release neuropeptides from their whole membrane surface predisposes neuropeptidesfor microdialysis experiments. This review outlines the special characteristics of neuropeptide signaling inrelation to other classes of neuromessengers. It further provides a survey of the application of the micro-dialysis technique for monitoring neuropeptide release patterns in laboratory rodents exemplarily for thetwo neuropeptides arginine vasopressin and oxytocin, discusses pros and cons of such experiments andoutlines perspectives for future neuroendocrine studies in rats and mice.© 2008 Elsevier Inc. All rights reserved.Contents1.2.3.4.5.6.7.8.9.NeuromessengersWhat are neuropeptides?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Modes of interneuronal communication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Listening to neuropeptides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Vasopressin and oxytocin and the Rosetta stone for neuroendocrinologyNeuroendocrine correlates of behavior. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Regulation of neuropeptide release . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Dissociation of central and systemic neuropeptide release . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Lessons learned . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Ways to go. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .125126126126128128129130131132133133. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10.1. NeuromessengersChemical signaling is a fundamental principle of communicationbetween neurons. The chemical compounds responsible for thisinformation transfer (here called neuromessengers) are known asneurotransmitters or neuromodulators, depending on whether theyaffect neuronal activity directly (neurotransmitters de- or hyperpolar-ize target neurons primarily by activating ion channel proteins) ormodulate the direct effects caused by neurotransmitter action(neuromodulators alter intracellular signaling primarily via G pro-tein-coupled receptors; Box 1). In a prototypic situation, neuromes-sengers arestored in vesicles and released frompresynaptic terminals.After binding to specific receptors at post- or presynaptic sites, theytrigger alterations in intracellular signaling. They are eliminated fromthe extracellular space either by (i) specific uptake mechanisms withsubsequent recycling and/or intracellular degradation, (ii) enzymaticextracellular cleavage or (iii) internalization of the receptor–ligandcomplex. Today, several different classes of neuromessengers aredistinguished (Table 1), including L-amino acids (e.g. glutamate,taurine, glycine, gamma amino butyric acid), D-amino acids (e.g. D-serine), biogenic amines (e.g. dopamine, noradrenaline, serotonin),purines (e.g. ATP, ADP), acetylcholine, gaseous messengers (e.g. nitricPharmacology, Biochemistry and Behavior 90 (2008) 125–134? Corresponding author. Max Planck Institute of Psychiatry, Neuroplasticity Group,Kraepelinstr.2,D-80804Munich,Germany.Tel.:+498930622652;fax:+498930622610.E-mail address: wotjak@mpipsykl.mpg.de (C.T. Wotjak).0091-3057/$ – see front matter © 2008 Elsevier Inc. All rights reserved.doi:10.1016/j.pbb.2008.03.017Contents lists available at ScienceDirectPharmacology, Biochemistry and Behaviorjournal homepage: www.elsevier.com/locate/pharmbiochembeh