Download Preclinical studies suggest that sexual steroids

Project Title: Studies of the effects of androgens on serotonergic neurons
Preclinical studies suggest that sexual steroids influence brain serotonergic
transmission, and that an important physiological role of brain serotonin neurons
is to modulate sex steroid-driven behaviour, such as aggression and sexual
activity. The notion that interactions between sex steroids and serotonergic
neurons are of importance for the regulation of emotions and behaviour also in
humans gain support from a variety of observations: a) most psychiatric
disorders assumed to be related to serotonin, e.g. since they respond to
treatment with serotonin reuptake inhibitors (SRIs), display a marked gender
difference in prevalence (F>M) and starts around or shortly after puberty; b) the
condition for which SRIs display the highest effect size, i.e. premenstrual
dysphoria, is clearly due to the influence of sex steroids on the brain; and c)
reduced libido is the most common side effects during long term treatment with
SRIs. Although it is hence well established that sex steroids, and most notably
testosterone, interacts with serotonergic neurons, and that this interaction is of
probable importance for a number of serotonin-related psychiatric disorders, the
molecular basis of these interactions remains to be clarified. In this project, this
issue will be addressed mainly in a series of experiments using normal and
genetically modified mice. We will a) use immunhistochemistry and neuronal
tracing to assess if sex steroid receptors are expressed by serotonergic neurons
and/or on neurons expressing postsynaptic serotonergic receptors and/or on
neurons that are part of a network where serotonergic neurons play an important
role, b) use quantitative RT-PCR to assess how the expression of serotoninrelated genes is influenced by gender, gonadectomy, sex hormone
administration, and genetical manipulation leading to a knock-out of androgen
receptors (ARKO mice), and c) use the offspring of ARKO mice with a so-called
floxP construction that have been bred with so-called Cre mice in order to study
how behaviour is influenced by a selective knock-out of androgen receptors in
serotonin neurons, or in nerve cells innervated by serotonin. In addition, the PhD
student will get insights about the ongoing clinical projects assessing a) the
possible influence of polymorphisms in sex steroid-related genes on various
serotonin-related traits, including personality and psychiatric morbidity, in
humans.
To apply, please contact:
Lars Westberg, PhD
Institute of Neuroscience and Physiology, Department of Pharmacology
Sahlgrenska Academy, University of Gothenburg
Box 431
405 30 Göteborg, Sweden
Ph: +46-31-786 3431
E-mail: [email protected]