Table Of Content0 1987. Elsevier Science Publishers B.V. (Biomedical Division)
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List of Contributors
R. Ader. Department of Psychiatry, University of Rochester School of Medicine and Dentistry,
Rochester, NY 14642, USA
M. Altstein, Laboratory of Neurochemistry and Neuroimmunology, NIH, NICHD. Bldg. 36. Rm. 2A21,
Bethesda, MD 20892, USA
S. Audigier, Centre CNRS-INSERM de Pharmacologie-Endocrinologie, 34094 Montpellier, France
E. C. Azmitia, Department of Biology, New York University, Washington Square East, New York,
NY 10003, USA
R. E. Ballieux, Department of Clinical Immunology, University Hospital, Utrecht, The Netherlands
W. A. Banks, VA Medical Center, Ochsner Medical Institutions and Tulane University School of
-
Medicine, Endocrinology SEC Medical Service, 1601 Perdido Street, New Orleans, LA 70146,
USA
C. Barberis, Centre CNRS-INSERM de Pharmacologie-Endocrinologie3,4 094 Montpellier, France
A. Beaudet, MNI, McGill University, Montreal, Quebec H3A2B4, Canada
J. C. Beaujouan, Chaire de Neuropharmacologie, INSERM 7.114, College de France, 11 place Marcelin
Berthelot, 75231 Paris Cedex S, France
R. F. Benus, Department of Animal Physiology, University of Groningen, Biological Center, P.O.
Box 14, 9750 AA Haren. The Netherlands
L. Bergstrthn, Chaire de Neuropharmacologie, INSERM U.114, College de France, 1 I place Marcelin
Berthelot, 75231 Paris Cedex 5, France
G. Bissette, Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA
A. Bjorklund, Department of Histology, University of Lund, Lund, Sweden
F. E. Bloom, Division of Preclinical Neuroscience and Endocrinology, Scripps Clinic and Research
Foundation, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA
M.-T. Bluet-Pajot, U. 159 INSERM, Unite de Neuroendocrinologie, Centre Paul Broca de I'INSERM,
2 ter. rue d'Alesia, 75014 Paris, France
B. Bohus, Department of Animal Physiology, University of Groningen, Biological Center, P.O. Box 14,
9750 AA Haren, The Netherlands
R. E. Brinton, The Rockefeller University, New York, NY 10021, USA
G. Chassaing. Laboratoire Chimie Organique Biologique, EA 455, Universite Paris, 6, place Jussieu,
75005 Paris, France
H. Clauser, U.159 INSERM, Unite de Neuroendocrinologie, Centre Paul Broca de I'INSERM, 2 ter,
rue d'AIesia, 75014 Paris, France
R. S. Cohen, Department of Anatomy, University of Illinois at Chicago, Chicago, IL 60612, USA
E. R. de Kloet, Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht.
Utrecht, The Netherlands
P. De Koning, Division of Molecular Neurobiology, Rudolf Magnus Institute for Pharmacology and
Institute of Molecular Biology and Biotechnology, University of Utrecht, Padualaan 8, 3584 CH
Utrecht, The Netherlands
A. J. H. de Ruiter, Department of Animal Physiology, University of Groningen, Biological Center, P.O.
Box 14, 9750 AA Haren, The Netherlands
D. de Wied, Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht,
Vondellaan 6, 3521 GD Utrecht, The Netherlands
S. Drouva, U.159 INSERM. Unite de Neuroendocrinologie, Centre Paul Broca de I'INSERM. 2 ter,
rue d'Alesia. 75014 Paris, France
R. H. Ehrensing, VA Medical Center, Ochsner Medical Institutions and Tulane University School of
Medicine, Endocrinology SEC - Medical Service, 1601 Perdido Street, New Orleans, LA 70146,
USA
A. Enjalbert. A.159 INSERM, Unite de Neuroendocrinologie, Centre Paul Broca de I'INSERM, 2 ter,
rue d'Alesia, 75014 Paris, France
J. Epelbaum, U.159 INSERM. Unite de Neuroendocrinologie, Centre Paul Broca de I'INSERM. 2 ter,
rue dAlesia, 75014 Paris, France
VI
D. S. Fokkema, Department of Animal Physiology, University of Groningen, Biological Center, P.O.
Box 14,9750 AA Haren, The Netherlands
F. H. Gage, Department of Neurosciences, UCSD, La Jolla, CA, USA
H. Gainer, Laboratory of Neurochemistry and Neuroimmunology, NIH, NICHD, Bldg. 36,
Rm. 2A21, Bethesda, MD 20892, USA
J. C. Garbutt, Department of Psychiatry, Biological Sciences Research Center 220-H, University of
North Carolina, School of Medicine, Chapel Hill, NC 27514, USA
W. H. Gispen, Division of Molecular Neurobiology, Rudolf Magnus Institute for Pharmacology and
Institute of Molecular Biology and Biotechnology, University of Utrecht, Padualaan 8, 3584 CH
Utrecht, The Netherlands
J. Glowinski, Chaire de Neuropharmacologie, INSERM U.114, Collhge de France, 11 place Marcelin
Berthelot, 75231 Paris Cedex 5, France
L. Gooren, Department of Endocrinology, Free University, Amsterdam, The Netherlands
M. R. Hanley, MRC Molecular Neurobiology Unit, University of Cambridge Medical School, Hills
Road, Cambridge CB2 2QH, UK
C. J. Heijnen, Department of Immunology, University Hospital for Children and Youth 'Het Wilhelmina
Kinderziekenhuis', Utrecht, The Netherlands
D. HervC, INSERM U. 114, Collhge de France, 75005 Paris, France
S. Jard, Centre CNRS-INSERM de Pharmacologie-Endocrinologie, 34094 Montpellier, France
J. Joosse, Biological Laboratory, Vije Universiteit, P.O. Box 7161, 1007 MC Amsterdam, The Nether-
lands
A. J. Kastin, VA Medical Center, Ochsner Medical Institutions and Tulane University School of
-
Medicine, Endocrinology SEC Medical Service, 1601 Perdido Street, New Orleans, LA 70146,
USA
P. Kitabgi, CNRS, Centre de Biochimie, Parc Valrose, 06034 Nice, France
J. M. Koolhaas, Department of Animal Physiology, University of Groningen, Biological Center, P.O.
Box 14,9750 AA Haren, The Netherlands
C. Kordon, U.159 INSERM, UnitC de Neuroendocrinologie, Centre Paul Broca de I'INSERM, 2 ter,
rue d'Altsia, 75014 Paris, France
G.L . Kovhcs, Institute of Pathophysiology, University Medical School, Szeged, Hungary
K. Kovhcs, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
P. Kragh-Serensen, Department of Psychiatry, Odense University Hospital, DK-5000 Odense C,
Denmark
R. R. F. Kuiters, Division of Molecular Neurobiology, Rudolf Magnus Institute for Pharmacology and
Institute of Molecular Biology and Biotechnology, University of Utrecht, Padualaan 8, 3584 CH
Utrecht, The Netherlands
P. W. Landfield, Department of Physiology and Pharmacology, Bowman Gray School of Medicine,
Wake Forest University, Winston-Salem, NC 27103, USA
S. Lavielle, Laboratoire Chimie Organique Biologique, EA 455, UniversitC Paris 6, place Jussieu,
75005 Paris, France
A. Lolk, Department of Psychiatry, Odense University Hospital, DK-5000 Odense C, Denmark
P. T. Loosen, Department of Psychiatry, Veterans Administration Medical Center, Nashville,
TN 37203, USA
A. Marquet, Laboratoire Chimie Organique Biologique, EA 455, UniversitC Paris, 6, place Jussieu,
75005 Paris, France
B. S. McEwen, The Rockefeller University, New York, NY 10021, USA
E. Mezey, First Department of Anatomy, Semmelweis University Medical School, Budapest, Hungary
E. Moyse, MNI, McGill University, Montrbal, Quebec H3A2B4, Canada
C. B. Nemeroff, Departments of Psychiatry and Pharmacology, Duke University Medical Center,
Durham, NC 27710, USA
C. Nyakas, Department of Animal Physiology, University of Groningen, Biological Center, P.O. Box 14,
9750 AA Haren, The Netherlands
M. Palkovits, First Department of Anatomy, Semmelweis University Medical School, Budapest,
Hungary
D. W.P faff, Department of Neurobiology and Behavior, Rockefeller University, 1230 York Avenue,
New York, NY 10021, USA
0. Ploux, Laboratoire Chimie Organique Biologique, EA 455, UniversitC Paris, 6, place Jussieu,
75005 Paris, France
A. J. Prange, Jr., Department of Psychiatry, Biological Sciences Research Center 220-H, University of
North Carolina, School of Medicine, Chapel Hill, NC 27514, USA
v11
A. J. A. Prins, Department of Animal Physiology, University of Groningen, Biological Center, P.O.
Box 14,9750 AA Haren, The Netherlands
R. Ravid, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam,
The Netherlands
B. Roozendaal, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam,
The Netherlands
W. H. Rostene, INSERM U.55, HBpital St. Antoine, 75012 Paris, France
M. Saffroy, Chaire de Neuropharmacologie, INSERM U.114, ColMge de France, 11 place Marcelin
Berthelot, 7523 1 Paris Cedex 5, France
Z. Sarnyai, Institute of Pathophysiology, University Medical School, Szeged, Hungary
A. Sarrieau, INSERM U.55, Hdpital St. Antoine, 75012 Paris, France
A. J. W. Scheurink, Department of Animal Physiology, University of Groningen, Biological Center, P.O.
Box 14,9750 AA Haren, The Netherlands
R. E. Siegel, Laboratory of Cell Biology, NIMH, Bethesda, MD 20892, USA
P. G. Smelik, Department of Pharmacology, Vrije Universiteit, Van de Boechhortstraat, Amsterdam,
The Netherlands
A. B. Steffens, Department of Animal Physiology, University of Groningen, Biological Center, P.O.
Box 14,9750 AA Haren, The Netherlands
D. F. Swaab, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam,
The Netherlands
G. Szab6, Institute of Pathophysiology, University Medical School, Szeged, Hungary
J. P. Tassin, INSERM U.114, College de France, 75005 Paris, France
G. Telegdy, Institute of Pathophysiology, University Medical School, Szeged, Hungary
Y. Torrens, Chaire de Neuropharmacologie, INSERM U.114, CollQge de France, 11 place Marcelin
Berthelot, 75231 Paris Cedex 5, France
E. Tribollet, Dkpartement de Physiologie, Centre Mkdical Universitaire Geneve, Geneva, Switzerland
I. J. A. Urban, Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht,
Vondellaan 6, 3521 GD Utrecht, The Netherlands
C. E. E. M. Van der Zee, Division of Molecular Neurobiology, Rudolf Magnus Institute for
Pharmacology and Institute of Molecular Biology and Biotechnology, University of Utrecht,
Padualaan 8, 3584 CH Utrecht, The Netherlands
G. A. van Oortmerssen, Department of Animal Physiology, University of Groningen, Biological Center,
P.O. Box 14,9750 AA Haren, The Netherlands
J. M. van Ree, Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht,
Vondellaan 6, 3521 GD Utrecht, The Netherlands
D. N. Velis, Department of Neurosurgery, Academic Medical Center, University of Amsterdam,
Amsterdam, The Netherlands
J. Verhaagen, Laboratory of Neuromuscular Diseases, Department of Neurology, Academic Hospital,
University of Utrecht, Nic. Beetsstraat 24, 3500 CG Utrecht, The Netherlands
W. M. A. Verhoeven, Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of
Utrecht, Vondellaan 6, 3521 GD Utrecht, The Netherlands
M. Vial, INSERM U.55, HBpital St. Antoine, 75012 Paris, France
J. P. Vincent, CNRS, Centre de Biochimie, Parc Valrose, 06034 Nice, France
M. H. Whitnall, Laboratory of Neurochemistry and Neuroimmunology, NIH, NICHD, Bldg. 36,
Rm. 2A21, Bethesda, MD 20892, USA
R. S. Williams, Neuropathology Laboratory, Shriver Center, Walton, MA 02154, USA
W. S. Young, 111, Laboratory of Cell Biology, NIMH, Bethesda, MD 20892, USA
J. E. Zadina, VA Medical Center, Ochsner Medical Institutions and Tulane University School of
-
Medicine, Endocrinology SEC Medical Service, 1601 Perdido Street, New Orleans, LA 70146,
USA
IX
Preface
Neuropeptides and Brain Function was the theme of the symposium held from
May 28-30, 1986 on the occasion of the 350th anniversary of the State University
of Utrecht. This theme was chosen since it forms the backbone of a long tradition
in CNS research carried out in the Rudolf Magnus Institute. This volume contains
the papers of the meeting, which provide a broad overview of the state of affairs in
neuropeptide research. It is divided into three sections, each devoted to the topic of
the day.
Part I on ‘Neuropeptides and Adaptation’, contains contributions on the role of
neuropeptides in brain mechanisms that underly adaptive processes in particular with
respect to their neuroendocrine, autonomous, behavioural, immunological and
evolutionary aspects.
Part I1 on ‘Neuropeptides: Basic Concepts’ concerns the more fundamental
aspects of neuropeptide research. It begins with the discovery of peptide effects on
brain and behaviour, and the formulation of the neuropeptide concept and ends with
a description of the influence of neuropeptides on electrical and molecular processes
in the brain.
Part 111 on ‘Neuropeptides, Therapeutic Implications and Future Developments’
focusses on the clinical significance of neuropeptides in the treatment of brain
diseases, and their role in brain aging, regeneration of damaged nerve tissue and
neural transplantation.
We are grateful to all who have contributed to the success of the Symposium. To
the chairmen Professors Angelucci, Lamberts, De Wolff, De Jong, Drago, Heijnen,
EndrBczi, Greven, Telegdy, Van Wimersma Greidanus, Lopts da Silva, Witter,
Mulder, Jenks, Brambilla, Bruinvels, Traber, Korf, Dorsa, Versteeg, Strand and
Boer, and to the speakers to whom we owe an unforgettable and exciting gathering.
We wish to thank Peter Burbach, Pierre de Graan, Cobi Heijnen and Dick
Veldhuis for the enthusiastic way in which they assisted in the local organisation of
the symposium. We would also like to thank Ms. Vera Visser and her coworkers from
QLT Convention Services, and Petra Bakels, Jan Brakkee, Ton van den Brink, Lia
Claessens, Joke Cox, Leo van Halewijn, Ed Kluis, Ad Ontskul and Ria van
Vlaardingen from the Rudolf Magnus Institute and the Institute of Molecular Biology
for their help.
Finally, without the support of the University of Utrecht ; The Pharmacologisch
Studiefonds, Utrecht; Organon International B.V., Oss; Koninklijke Nederlandse
Akademie van Wetenschappen, Amsterdam; Troponwerke GmbH, Cologne, FRG;
Fidia Pharmaceutical Co., Abano Terme, Italy and the VVAA N.V. Utrecht, the
organisation of this symposium would not have been possible.
E. R. de Kloet, V. M. Wiegant and D. de Wied
Rudolf Magnus Institute for Pharmacology,
Utrecht. The Netherlands
E. R. de Kloet, V.M. Wiegant and D. de Wied (Eds.)
Progress in Brain Research. Vol. 12
3
0 1987 Elsevier Science Publishers B.V. (Biomedical Division)
CHAPTER 1
Adaptation and brain function
P.G. Smelik
Department of Pharmacologv, Vnje Universiteit. 1081 BT Amsterdam, The Netherlands
Introduction Adaptation should be considered as a con-
tinuous process in which there is a permanent
To introduce the theme of this first day of our interplay between the organism and its environ-
Symposium Neuropeptides and Brain Function, it is ment. Since the environment is changing con-
my task to focus on the role of the central nervous stantly the organism has to adjust its behaviour
system in adaptation. and its functioning permanently. Although it is
Although it appears that there is no great need true that during evolution organisms became
for a definition of the word ‘brain’, the word more independent of physical and chemical varia-
‘adaptation’ could call for some comment. bles in the environment, it can also be said that
Looking back in history, adaptation has often higher organisms became more dependent on the
been connected with the preservation of homeo- psycho-social environment.
stasis, in the sense that any stimulus which would In humans, adaptation has primarily the con-
cause a deviation from pre-set values would also notation of adjustment to social variables. The
cause an immediate correction in the opposite most demanding environmental challenges for
direction in order to preserve a constancy of the humans are not of a physical nature but are
internal environment. Such an interpretation is changes which have a profound emotional impact
not untrue but it is very limited. It seems that in (e.g. loss of a partner, failure of a career, hostility
many cases adaptation consists in changing set- or loneliness). Adaptation involves coping with
points in order to meet new demands. problems and sorrow.
Another somewhat too limited use of the word
adaptation occurs when it is connected with The limbic structures
extreme challenges such as mutilation, intoxica-
tion or severe illness. When Hans Selye intro- If adaptation indeed includes behavioural and
duced the idea that the organism responds to emotional adjustment, it is obvious that the
stressful stimuli with a standardized hormonal entire brain is involved in adaptation. Adaptive
reaction, i.e. a pituitary-adrenocortical activation, functions include integration of sensory informa-
he called this the ‘General Adaptation Syndrome’. tion, learning, planning of behaviour, motor re-
This syndrome consisted of the triad of symp- sponses and neuroendocrine adjustment. One
toms : adrenal hypertrophy, involution of the thy- may wonder whether it is justified to consider
mus and gastrointestinal ulcers. Nowadays we certain brain structures or functions as specific for
are aware that this syndrome is rather a sign of adaptation. It can be argued that the limbic struc-
maladaptation than of adaptation: in such cases tures are essential for adaptation processes. If
something must definitely have gone wrong! their functions are to be summarized in one sen-
4
tence, it can be said that the limbic system ‘keeps harmless or safe; in this case the arousal reaction
us on the beam’ (Cotman and McGaugh, 1980). will be extinguished and the stress response shut
The main divisions of the limbic system are the off. Conversely, it may turn out that the expect-
limbic midbrain and the limbic forebrain. Their ancy is uncertain or even quite negative, that real
role in adaptation can only be characterized by harm or danger will be encountered. The arousal
giving a highly schematic view. state will be maintained, and it will be anticipated
The limbic midbrain system induces, via the that defense actions (e.g. fight or flight) have to be
ascending reticular activating system (ARAS), an performed.
increase in general alertness or vigilance when any In the planning of the behavioural response to
stimulus is perceived which may be significant for be made the frontal lobe (which can also be con-
survival. Such a stimulus may be harmful, sidered as part of the limbic system) integrates
threatening or rewarding, but attention or curio- and controls all the information processing and
sity and readiness for action are increased in every associates sensory information flow with the
instance. The physiological systems subserving emotional input from the limbic areas. There are
action (e.g. fight or flight) are activated, mainly important direct connections between the pre-
through the sympathetic system. frontal cortex and the registration of aversive
This arousal reaction (as it is now generally stimuli in the midbrain limbic structures.
called) can be considered as the primary stress Once the judgement has been made, a decision
response or alarm reaction of Selye. It is an about the type of behavioural action is taken. The
unconditioned response, and also comes close to amygdala plays a crucial role in this performance,
Pavlov’s orientating reflex. An important conse- be it attack or avoidance. The purpose is to per-
quence of this modem view is that such arousal form an adequate behavioural response in order
reactions are part of everyday life both in animals to remove the imminent danger.
and in man. It means that the so-called stress Another possibility may be that it is not (yet)
response is not always an emergency reaction but clear which action must be taken, e.g. when the
a primary adaptive reflex answer to biologically situation is novel or unpredictable or when no
significant signals. adequate response can be found or the response
If such a signal is presented, a decision has is obstructed (helplessness). In such a case, the
to be taken whether a behavioural response best decision seems to be to do nothing. This is
should be initiated, and if so, of which kind of known as ‘freezing’ or behavioural inhibition
action is to be performed. For this decision to be (Gray, 1982). The septo-hippocampal system
taken, the situation has to be evaluated. This is plays an essential role in this strategy. It is charac-
done primarily within the limbic forebrain system. terized by the maintenance of a high level of
Here a novel situation is compared with earlier arousal, high alertness and anxious anticipation.
experience and the significance of the stimulus is All defense mechanisms are in a state of alarm,
estimated by matching stored information with the emotional state is tense and anxious and
new information (Sokolov 1963). The hippocam- feelings of helplessness are prevalent. It is felt,
pus plays a crucial role in this process: it receives nowadays, that this is the most stressful situation
information from the stores in the temporal lobe in both mammals and man.
(‘memory retrieval’), it serves as a spatial map for Essential to the solving of this problem is
orientation in the environment and it may take whether the right behavioural solution can
decisions or make predictions about expected eventually be found. An adequate behavioural
events. response will resolve anxiety, will extinguish the
The result of this appraisal process can be arousal state and attenuate the neuroendocrine
two-fold: the signal may be recognized as being activation state. This means that adequate adapt-
5
reticular formation limbic system
AROUSAL
adequate
neuroendocrine
response UNCE RTA I NT Y
ANXIETY
Fig. 1. Schematic representation of events involved in adaptive responses.
ation can be obtained by adequate coping be- systems are involved, our knowledge of which is
haviour. Coping eventually reduces the pathologi- still fragmentary. Neuronal systems are charac-
cal consequences of stressful situations; con- terized by their type of neurotransmission, and
versely, helplessness, conflict and frustration ag- only a small proportion of such systems has been
gravate stress symptoms (Levine et al., 1978). sufficiently analysed to allow preliminary con-
This survey (Fig. 1) demonstrates that the lim- clusions. Relatively speaking, most of the infor-
bic brain is essential in the management of adapta- mation available concerns systems which are
tion to environmental challenges, not only in the monoaminergic. These are neurons which convey
sense that certain brain structures are involved in their information through the release of nor-
specific adaptive mechanisms, but also in the adrenaline, serotonin or dopamine. Much less is
sense that the emotional and behavioural re- known about the role of neurons which produce
sponses appear to be crucial for the success of neuropeptides as messenger substances. Here the
adaptation. available evidence is virtually restricted to so-
called releasing factors and to opiate peptides.
Neuronal systems involved in adaptation The now classical monoaminergic systems
have been identified by using histochemical me-
When we take a closer look at the neuronal sys- thods. Much is known about synthesis, storage
tems which are involved in processing relevant and release of these transmitters and extensive
information pertinent to the adaptation mechan- pharmacological manipulation of their function is
ism, we are hampered by the fact that numerous possible.
6
It appears that the noradrenergic system is stimuli, in circadian rhythms and sleep. The im-
primarily involved in the alarm or arousal pression is that it is involved in controlling emo-
reaction. A central position in this mechanism is tional reactions to unpleasant experiences; it is
occupied by the cell group in the locus coeruleus supposed to inform the limbic system that a sti-
in the dorsal tegmentum, projecting to the main mulus or situation is associated with punishment,
parts of the limbic system and the cortex. The and it may specifically mediate the septo-hippo-
projections are rather diffuse and appear to sub- campal behavioural inhibition system. It may try
serve general alertness or vigilance. The general to counteract negative emotional experiences by
message which this assemblage seems to convey generating relaxation, even satisfaction and iner-
is: ‘be aware, this may be important and needs tia. It gives the impression that in a sense it is the
careful checking’ (Gray, 1982). It has been sug- central counterpart of the parasympathetic system
gested that ‘learned helplessness’ situations lead in the periphery. These characteristics may be the
to a motor activation deficit through depletion of reason that the serotonin system has always been
noradrenaline stores (Glazer and Weiss, 1975). associated with mood, and that depression has
Another important noradrenergic pathway something to do with inadequate functioning of
courses ventrally to the hypothalamus, mediating this system.
aggressiveness and eating/drinking behaviour. The dopaminergic system can be divided into
Descending projections convey control over auto- several subsystems, of which the meso-limbic and
nomic regulations (e.g. cardiovascular). meso-cortical neurons are of main interest for
The serolonergic system has its cell groups adaptation. The meso-limbic projections run
mainly in the raphe nuclei, and also projects rather from the ventral tegmentum area to the septum
diffusely to higher structures. Its functions are less and the,N. accumbens and are involved in the
easy to summarize. We know that it plays an processing of rewarding stimuli and in motivation
important role in processing of pain and aversive of behaviour (Iversen, 1977 ; Willner, 1983). This
TABLE 1
Involvement of monoaminergic systems in adaptive responses
Possible functions of forebrain monoaminergic systems
When activated When inhibited
~ ~
General unspecific arousal Sedation
Alertness (scanning) Low awareness
Noradrenaline Tense anticipation Apathy
Readiness for action Psychomotor inhibition
Aggressiveness Taming
Satisfaction Negative mood
Relaxation Disturbed diurnal rhythms
Serotonin Diurnal rhythms Insomnia
Motor inhibition in pain and Restlessness
aversive stimuli
Compulsive motor behaviour Disturbance motor coordination
Motivation purposeful behaviour Emotional indifference
Dopamine
Facilitation reward system Inhibition reward system
Selective attention Inability to focus attention
1
system facilitates the initiation of goal-directed in reward mechanisms, in eating behaviour and in
action; its inhibition leads to emotional indif- ideation is beyond doubt. There are some indica-
ference and lack of initiative. The meso-cortical tions that they do so by modulating the release
part projects mainly to the frontal cortex, which of monoaminergic transmitters. It seems that the
is crucial for judgement and planning of behaviour physiological role of opioid peptides is mainly
(Glowinski et al., 1977). Of special interest is the restoration of the balance between feelings of
dopaminergic projection to the prefrontal cortex happiness and unhappiness. This is a system of
which is concerned with focussed attention. If paramount significance for animal behaviour.
important novel or threatening stimuli are con- Generally speaking, it can be said that animal
ducted to the prefrontal cortex, attention is fo- behaviour is guided mainly by avoiding aversive
cussed on the stimulus and will not be diverted to stimuli and seeking gratifying stimuli. Without
other simuli. Persistent hyperactivity of this sys- this reward-punishment system an animal would
tem may account for the compulsive preoccupa- not avoid danger or injury and would not pursue
tion with certain objects or ideas seen in psy- eating or mating. The fact that opioid release can
choses and which can be released by anti- bring about such intense gratification that the
dopamine drugs (neuroleptics). organism can become addicted to its effects
This section is summarized in Table 1 and Fig. 2. demonstrates how powerful the impact of such
Much less can be said about peptidergic sys- systems on behaviour can be.
tems, because it is still difficult to manipulate A number of peptidergic systems are known to
these systems selectively. Nevertheless, it can be play a role at the hypothalamic level. The hypo-
accepted that the opioid peptide systems play an thalamus can be considered as a part of the limbic
important role in the modulation of many adaptive system, but then as a gateway to the periphery. It
functions. Their involvement in pain perception, receives arid coordinates a wealth of information
