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Biologische Psychologie III
Teil 3
Vorlesungsunterlagen, WS 2004/05 Univ. Prof. Dr.
Wolfgang Klimesch
Teil 3 Emotionen Aggression und Testosteron
Emotionale Störungen Stress
Sexualhormone und Verhalten.
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3.8 Aggression and Testosterone
Hormones/Transmitters primarily involved in
aggression - Testosterone and Serotonin (c.f
Nelson, R. J. S. Chiavegatto (2001). Molecular
basis of aggression, TINS, 24(12), 713- 719.
T
Ag
S
Ag
Many other substances (like histamine, HA, or
Vasopressin) also play an important role, but
appear to be effective primarily via modulation
of serotonin
HA
Ag
S
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3.8.1 Some basics about Testosterone (T) - T is
made in the Leydig cells of the testes and to a
much smaller degree in the cortex of the adrenal
glands. - The release of T occurs in spurts
(in the range of minutes) and is triggerd by GnRH
of the hypothala-mus which causes the anterior
pituitary to release LH and FSH LH Testosterone
production in Leydig cells and production of
Leydig cells during development FSH Stimulates
spermatogenesis
- Concentration in male blood 1/100.000 gram
of T per liter Note 1 nanogram 10-9 g 10
ng 10-8 g 1 picogram 10-12 g
(10 ng 10-8 g) 10 - 4 per ml 10 - 4
10 4 pg per ml
10-5 g liter
10-5 g 10-3 10 ng liter 10-3
milliliter


- Concentration of T in male saliva is about
1/100 that of T in blood
Or considering that 1ng 1000 pg 10000 pg
10-2 100 pg milliliter
ml
10 ng 10-2 10 ng 10-2 10 ng
milliliter dl 10-2
dl



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3.8.2 Testosterone, Dominance and social behavior
From Ewert, J. P. (1998), Neurobiologie des
Verhaltens, Bern Hans Huber
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Rose et al., 1971
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Rose et al., 1971
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Rose et al., 1971
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Testosterone (pg/ml)
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Testosterone and Mens Marriages
TABLE 3 Zero Order Correlations between
Testosterone and Mediating Variablesa
4
5
6
7
1
2
3
1. Testosterone
2. Age
-.18
3. Education
-.10
.16
4. Income
-.10
.17
.34
5. Occupational status
-.09
.16
.48
.28
-.13
-.14
6. Alcohol
.12
-.16
-.17
7. Trouble with law
.13
-.17
-.17
-.23
-.12
.52
.09
8. Unemployed
-.10
-.13
-.42
-.12
.19
.26
a All coefficients are statistically significant
at the .01 level or beyond.
Booth, A. Dabbs, J.M. (1993). Testosterone and
Mens Marriages.Social Forces, 72(2), 463-477.
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Mean salivary testosterone concentrations among
male and female subjects before and after sexual
activity and before and after no sexual activity.
Log Testosterone (ng/dl)
Dabbs, J.M., Jr. Mohammed, S. (1992). Male and
Female Salivary Testosterone Concentrations
Before and After Sexual Activity
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Morning
Evening
Dabbs, J.M. de la Rue, D. (1991). Salivary
Testosterone Measurements among Women Relative
Magnitude of Cardian and Menstrual Cycles.
Hormone Research, 35, 182-184.
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Hellhammer et al. 1985
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Klimesch, Bio III, WS 03
References TESTOSTERONE, Dominance and
Aggression   Albert, D.J., Walsh, M.L., Jonik,
R.H. (1993). Aggression in humans What is its
biological foundation? Neuroscience and
Biobehavioral Reviews. 17, 405-425.   Archer, J.
(1994). Male Violence. London Routledge   Booth,
A., Dabbs, J.M. (1993). Testosterone and mens
marriages. Social Forces, 72(2), 463-477.
  Booth, A., Shelley, G., Mazur, A., Tharp, G.,
Kittok, R. (1989). Testosterone and winning and
loosing in human competititon. Hormones and
Behavior, 23, 556-571.   Borkenau, P.
Ostendorf, F. (1993). Costa und McCraes
NEO-Fünf-Faktoren Inventar (NEO-FFI),
Handanweisung. Göttingen Hogrefe.   Dabbs, J. M.
Jr., Morris, R. (1990). Testosterone, social
class and antisocial behavior in a sample of
4,462 men. Psychological Science, 1,
209-211.   Fahrenberg, J., Hampel, R. Selg, H.
(1988). Das Freiburger Persönlichkeitsinventar
(FPI-A1). Göttingen Hogrefe.   Mazur A. Booth,
A. (1998). Testosterone and Dominance in Men.
Behavioral and Brain Sciences, 21, 353
397.   Mazur, A., Halpern, C. Udry, J. (1994).
Dominant looking male teenagers copulate earlier.
Ethology and Sociobiology, 15, 87-94.   Mazur A.
Lamb, T. (1980). Testosterone, status, and mood
in human males. Hormone and Behavior, 14,
125-146.   Möstl, E., Meyer, H. H.D., Bamberg, E.
and von Hegel, G. (1987) Oestrogen determination
in feces of mares by enzyme immunoassay on
microtitre plates. Proc. Symp. Analysis Steroids,
Sopron Hungary 219 224.   Pargman, D. Baker,
M.C. (1980). Running high enkephalin addicted.
Journal of Drug Issues, 10, 341-349.   Peele, S.
(1985). How can addiction occur with other than
drug involvement. British Journal of Addiction,
80, 23-26.   Kemeny, D.M. (1991). A Practical
Guide to ELISA. Oxford Pergamon Press.   Nelson,
R.J. (1995). Behavioral Endocrinology.
Massacusetts Sinauer Associates,
Inc.   Panksepp, J. (1998). Affective
neuroscience. New York Oxford University
Press.   Rose, R. M., Holaday, J. W.,
Bernstein, I. S. (1971). Plasma testosterone,
dominance rank and aggressive behavior in male
rhesus monkeys. Nature, 231(11),
366-368.   Rubinow, D.R., Schmidt, P.J. (1996).
Androgens, brain, and behavior. American Journal
of Psychiatry, 153 (8), 974-984.   Townsend, J.
M. (1993). Gender differences in mate preferences
among law students. Journal of Psychology, 127,
507-528.
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Klimesch, Bio III, WS 03
4. The ascending dopaminergic system and
emotional disorders 4.1. Schizophrenia The
traditional view held that excessive
dopamine-mediated neurotransmission underlies
schizophrenia. Antipsychotic drugs are
antagonists of D2-like dopamine receptors (D2,
D3, D4) and, thus, reduce dopamine-mediated
neurotransmission. New evidence, however,
suggests that D1-like receptors (D1, D5) play a
more critical role in patients with negative
symptoms. By downregulating D2-like dopamin
receptors, antipsychotic drugs may lead to a
compensatory upregulation of D1-like receptors.
Okubo et al. (1997 Nature, Vol. 385, p. 634-
636) have used positron emission tomography to
show that there are reduced levels of D1-like
dopamine receptors in the prefrontal cortex (PFC)
even in drug naive patients with schizophrenia.
D2-like receptors which are found primarily in
the striatum are not reduced. The synaptic
organizatin of the prefrontal cortex is shown
schematically in the Figure below (after Nestler,
1997, Nature, Vol. 385, p. 578-580). Note that
the expression of D1-like receptors is up to ten
times higher than that of D2-like receptors.
These receptors are found primarily on the
dendritic spines of prefrontal pyramidal neurons.
Here, glutamate-mediated inputs from other
pyramidal neurons and thalamic neurons can easily
be modified.
D2-like receptors D2 and D3 receptors are
present at lower levels in the preforntal cortex,
and they may be expressed in several neuronal
elements. D4 receptors are enriched in
GABA-containing interneurons, Glu, glutamate,
GluR, glutamate receptors GABA, ?- aminobutyric
acid DA, dopamine 5-HT, serotonin.
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Only negative symptoms correlate (negatively)
with the number of D1R. Neither the total BPRS
(Brief Psychiatric Rating Scale) score nor the
score for positive symptoms (e.g.,
hallucinations) show a significant relationship.
Conclusion The activating influence of the
ascending dopaminergic sysrtem is primarly
mediated by D1-like receptors in the prefrontal
cortex. In healthy subjects these receptors are
up to 10 times more frequent than D2-like
receptors and are reduced in schizophrenics with
negative symptoms.
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4.2. Depression and the dopaminergic
system Explanation of depressive and psychotic
disorders on the basis of an imbalance in
DA-activity in three nested feedback loops. After
the meanwhile classical work of Swerdlow Koob
(1987, BBS, 10, 197- 245).
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Step 1 Activation starts in Thalamo-Ctx feedback
loop. Nucl. Acc inhibits Ventral Pallidum and
Spiny I matrix.
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Step 2 Ventral Pallidum DM Thalamus and Ventral
Tegmentum get disinhibited
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Step 3 Nucl. Accumbens is inhibited. This
inhibition overrides excitation from Limbic Ctx).
Ventral Pallidum gets disinhibited which in turn
leads to inhibition of Thalamo-Ctx feedbackloop
and Ventral Tegmentum.
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DEPRESSION Step 2 Ventral Pallidum is inhibited
DM Thalamus and Ventral Tegmentum get
disinhibited. Due to a lack of DA, Ventral
Tegmentum remains silent Step 3 Ventral Pallidum
will not be disinhibited, Loop I will not be
disrupted.
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PSYCHOSIS Step 2 Ventral Pallidum is inhibited
DM Thalamus and Ventral Tegmentum get
disinhibited. Due to excessive dopaminergic
excitability, Ventral Tegmentum becomes
excessively active. Step 3 Ventral Pallidum will
be massively disinhibited, Loop I will be
disrupted powerfully.
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4.4 The basal ganglia, motor behavior and the
nigro-striataldopaminergic stystem
PET-scans of normal subjects and patients with
Morbus Parkinson are shown below (from Heiss,
W.D. Würker, M., 1999. Möglickeiten und Grenzen
funktioneller bildgebender Verfahren beim
Parkinson-Syndrom. Nervenarzt (Suppl. 1) 70,
S2-S10.) Clinical sym-ptoms appear after a loss
of more than 50 of the dopamin-ergic neurons in
the nigro -striatal system
Glucose metabolism
Dopamin
D2-Receptors
Normals M.P. untreated
M.P. treated
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The extrapyramidal system and the basal
ganglia Over the years, the term extrapyramidal
motor system was replaced by the term basal
ganglia. Due to differences in the use of the
latter term, different brain areas are comprised.
According to Nauta Feirtag (1986) it comprises
the corpus striatum, the subthalamic nucleus
(part of the tegmentum) and the substantia nigra.
In a much narrower sense striatum and basal
ganglia are sometimes used synonymously.
The Striatum comprises - Nucleus caudatus -
Nucleus accumbens - Putamen - Globus pallidum
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N. Caudatus
Globus Pallidus
Putamen
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Basal Ganglia Some basic connectivity (cf.
Marin, O., Smeets, W. Gonzalez, A. (1998).
Evolution of the basal ganglia in tetrapods a
new perspective based on recent studies in
amphibians. TINS, 21 (11), 487-494. The basal
ganglia play a crucial role in motor functions,
in particular in the planning, initiation and
execution of movement.
CORTEX
Striatum
Thalamus
Sensory Information
Subthalamus
Superior Colliculi
Pretectal Region
Substantia nigra pars compacta
Substantia nigra pars reticulata
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4. 3 Stress, fear and the immune system
Medial, sagittal view of the hypothalamus (in
color) and pituitary gland (dt. Hypophyse)
Paraventricular nucleus Dorsal hypo-
Posterior hypo-
thalamic area
thalamic area
Preoptic area Anterior hypo- thalamic
area Suprachiasmatic n. Supraoptic
nucleus Chiasma opticum
Dorsomedial nucleus Ventromedial
nucleus Lateral Mamillary nucleus Medial
Descending input into primary plexus
Nervus opticus
Secundary plexus
Anterior pituitary
Posterior pituitary
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Hypothalamus Pituitary Adrenal Axis, HPA-axis
In response to stress, the hypothalamus secrets
the corticotropin-releasing hormon (CRH) into the
hypophyseal portal system. In response to CRH the
anterior hypophysis secrets the
adrenocorticotropin hormone (ACTH) into the
bloodstream
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The HPA-axis and Fear CRH activates the locus
ceruleus
Stress
Amygdala emotional memory for fight flight
behavior/situations
Fibers of CRH secreting neurons
CRH
ACTH
Adrenal Gland
Stress CRH Fear
Cortisol
Cortisol
Immune System
Immune system
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The HPA-axis, stress and the interaction with
the immune system
Stress
Amygdala emotional memory for fight flight
behavior/situations
ACTH
Cytokines are messenger (protein) molecules of
the immune system They stimulate the hypothalamus
Adrenal Gland
N. of Sympathetic NS
Cortisol
Positive feedback cycle that provides the basis
of a strong immune response
Immune system
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The HPA-axis, stress, the immune system and
depression See e.g., Sternberg, E.M. Gold, P.
W. (1997). The mind body interaction in disease.
SciAm, Special Issue, Vol. 7 (1), 8-15.
Stress
Amygdala emotional memory for fight flight
behavior/situations
ACTH
Cytokines are messenger (protein) molecules of
the immune system They stimulate the hypothalamus
Adrenal Gland
N. of Sympathetic NS
Cortisol
Positive feedback cycle that provides the basis
of a strong immune response
Immune system
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In many types of depression, a chronic
overactivation of the HPA-axis and an increase in
inflammatory diseases (e.g., arthritis) can be
observed. It is known that imipramine (which
enhances ctecholamine activity) leads to a
downregulation of HPA-axis functions.
Lowered Upregulation
Downregulation catecholamine of
HPA-axis of
Illness level
functions immune system
Increase in Downegulation
Upregulation melatonin level of
HPA-axis of
Allergy during SAD unctions
immune system
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5. Sex hormones and behavior
Sex Differentiation What makes you male or
female?
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Rats gastation period 21 days Gonadal
differentiation completed at about 10 days after
birth.
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Experimental Protocol for determining
organizational versus activational effects of
androgens on sexually dimorphic mating behavior
in rodents.
No
Remove gonads before day 10 ?
No
Yes
No
Yes
Inject with testosterone before day 10 ?
No
Yes
Yes
Yes
Remove gonads in adulthood ?
Yes
No Yes
No Yes
Inject with testosterone in adulthood ?
No Yes
No Yes
No Yes
No No
No Yes
Male-typical behavior ?
No Yes
No No
No Yes
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Chemical pathway of sexual steroids, fetal
testosterone and DHT
Male Development
Female Development
XY Chromosome
XX Chromosome
CHOLESTEROL
PROGESTERONE

Female Brain
TESTOSTERONE
Male Brain
Enzyme 5-?-reductase
Enzyme Aromatase
Male Body
DHT
ESTROGENE
Female Body
Anmerkung Bei der normalen Entwicklung des
weibl. Fötus müssen Östrogene direkt aus
Testosteron enzymatisch umgesetzt werden. DHT
darf nicht gebildet werden.
Bestimmte Regionen im Gehirn, vor allem im
Hypothalamus und im Limbischen System (hier vor
allem die Amygdala) haben Rezeptoren für
Testosteron. In kritischen fötalen
Entwicklungsphasen Werden diese Rezeptoren
ausgebildet und reagieren auf Testosteronausschütt
ung durch differenziertes Wachstum. Fehlt die
Testosteronausschüttung, dann sterben diese
Neurone ab und das Gehirnd wird Weiblich
ausgebildet (vgl. dazu Untersuchungen bei Ratten
zur POA (preoptic area), die beim Menschen dem
INAH (intermediate nucleus of anterior
hypothalamus) entspricht). Eine Übersicht zu
Gehirnregionen in den Testosteron- und
Östrogenrezeptoren vorliegen ist z.B. In
Nieuwenhuys (1985, Fig. 56, S 184) zu finden.
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FSH
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LH
Follicular Phase
Theca externa Theca interna develops receptors
produces androgens from cholesterol for
LH Granulosa cells develop receptors
produce estrogenes from androgenes for FSH
Follicle
LH
FSH
Ovulation
Theca externa Theca interna produces androgens
from cholesterol
Granulosa cells produce
estrogenes from androgenes, develop receptors
produce progesterone for LH
Follicle
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Relationship between substance level and
receptor density Aspects related to
addiction
A) Tonic Level No Change
Receptor density
Substance level
B) Tonic Level Chronic Change
Receptor density
Substance level
CASE 2 A high substance level is related to low
receptor density
CASE 1 A small substance level
is related to high receptor density
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C) Phasic Change The impact of a phasic change
in CASE 1 2 CASE 1 A small phasic change in
the substance level has a large effect. CASE 2 A
small phasic change has little or no effect
(addiction).
C1) If we assume that a person has a low level in
e.g., endorphine, a situation changing the
substance level has a large effect.
Examples - A non-dominant individual, put in a
dominant situation experiences a large change. -
A non-sensation seeking individual, put in an
exciting situation experiences a strong feeling
Receptor density
B) Tonic Levels related to CASE 1 2
Substance level
C2) If we assume that a person has a high level
in e.g., endorphine, a situation changing the
substance level has little effect.
Receptor density
Examples - A dominant individual, put in a more
dominant situation experiences no or only a
small change. - A sensation seeking individual,
put in an exciting situation experiences no or
only little excitement.
Substance level
D) A strong phasic change may lead to a tonic
change
Receptor density
Substance level