Function and pharmacology of monoamine neurotransmitters

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Dr S. Clare Stanford
Reader in Experimental Psychopharmacology
Tel: 020 7679 3731
Email: c.stanford@ucl.ac.uk

Lab members:

  • Ms Katharine Pillidge
  • Mr Ashley Grimme

Research


The so-called 'monoamine neurotransmitters', which include dopamine, noradrenaline, adrenaline and serotonin, are released from neurones in both the brain and peripheral nervous system. The function of the monoamines is not clear but they are thought to have a crucial role in arousal, emotion and cognition. Certainly, drugs that augment the effects of monoamines on their target tissues are used to treat psychiatric disorders such as anxiety, depression and schizophrenia. The major aim of our research is to explain how the brain regulates monoamine transmission and to understand their influence on mood and behaviour.

The main focus of our research has been to understand the role of monoamine transmitters in the therapeutic effects of antidepressants. Our key findings revealed that antidepressants (even drugs known as ‘Selective Serotonin Reuptake Inhibitors’) actually modify the function of both serotonin and noradrenaline in vivo, regardless of their selectivity in vitro. This fundamental shift in emphasis, from serotonin as a key factor in ‘antidepression’, to the importance of interactions between all three monoamines, and their downstream consequences, is still amajor focus of research in this field. 

We have also compared changes in monoamine transmission induced by the anti-obesity drug (and the monoamine-releasing agent), d‑amphetamine, and the reuptake inhibitor, sibutramine. We have characterised not only qualitative differences in the effects of these two drugs but also striking differences in latency of the monoamine responses to these compounds. It is these differences in latency that explain why d‑amphetamine is addictive but sibutramine is not. This work made a vital contribution to an application for a product licence submitted (to the FDA and, subsequently, worldwide) by our industrial sponsor. Until recently, sibutramine was the only centrally-acting drug licenced for treatment of obesity.

Our long-standing interest in the mechanism of action of antidepressant drugs led to an investigation of the neurochemical and behavioural abnormalities of NK1R-/- mice, which lack functional receptors for the neuropeptide, substance P. We started studying these mice because their abnormal behaviour supposedly resembles that of wildtype mice that have been given an antidepressant drug. In the course of this work, which was carried out in collaboration with Professor Stephen Hunt of this department, we made the exciting discovery that NK1R‑/- mice express the core features of Attention Deficit Hyperactivity Disorder (ADHD). These include hyperactivity, which is prevented by d-amphetamine, inattentiveness and impulsivity as well as striking abnormalities in monoamine transmission in the brain.

This work in mice has been complemented by genetic studies of patients with ADHD (carried out in collaboration with Professor Hugh Gurling, Molecular Psychiatry). This translational research, which has linked directly our findings in mice and humans, has led to the discovery of a novel target for drug treatment of ADHD, which is a major focus of our current research.

Biography

Clare Stanford graduated in physiology from UCL and then carried out research for a DPhil in the University Laboratory of Physiology at Oxford university. She was awarded a university scholarship to enable her to stay on as a postdoc and to continue her research on the regulation of central and peripheral noradrenergic transmission. This was followed by a Demonstratorship in the same department and her appointment as the first woman Fellow of Exeter College. She has held a visiting research fellowship at the University of Bergen, Norway and was appointed to a tenured lectureship in pharmacology at The Middlesex Hospital Medical School. She moved to this department in 1987 and is currently a Reader in Experimental Psychopharmacology.  She was a member of the Senate and also of Council of the University of London where she served as chairman of the Subject Area Board in Life Sciences for six years. She has edited four books, contributed nearly 20 chapters to other books and has been a senior author on over 80 peer-reviewed papers.

As well as being a Past President of the British Association for Psychopharmacology (BAP), she is the current President of the Laboratory Animal Science Association (LASA).   She is an Editor of several international journals (British Journal of Pharmacology, Pharmacology Biochemistry and Behavior, Journal of Psychopharmacology, International Journal of Neuropsychopharmacology) and has served on the National Centre for the 3Rs (NC3Rs) grant panel. She is Chairman of a working group, set up by the NC3Rs, to promote improvements in experimental design and data analysis in whole animal science.

Clare was also responsible for setting up a series of training (CPD) modules, leading to the BAP Certificate in Preclinical Psychopharmacology. This pioneering and highly successful programme (now in its 15 th  year and emulated by other societies) attracts delegates from all over Europe, as well as the UK. It  is aimed at postgraduate students, postdoctoral workers and established scientists moving into psychopharmacology from other disciplines (for more information, see:  www.bap.org.uk).   

She is invited regularly to give talks on welfare and ethics in psychopharmacology but also often talks to schools and other groups (e.g., clinicians, the police and the DANA centre) to encourage public interest in psychopharmacology. She has made many media appearances including ITV, Channel 4, Sky TV, Radio 4 and the World Service

Research Activities

Genetics and Neurobiology of Mental Illness

Role of central monomine systems in regulation of mood and behaviour

Education Description

Major contributions to the teaching of neuropharmacology (especially psychopharmacology) to second and third year BSc and BMS students.

The organiser and sole lecturer for a third-year course in Psychopharmacology (comprising more than 20 lectures in topics ranging from stress and psychotic disorders to neuroethics

Contributions to the MSc Neuroscience course, focussing on the neurobiology of mood and behaviour Founder and Course Director of the British Association for Psychopharmacology Certificate in Preclinical Psychopharmacology

UCL Collaborators

Prof Hugh Gurling; Dr Andrew Mcquillin; Prof Steve Hunt

External Collaborators:

Professor David Stephens (University of Sussex)

Dr Stuart Peirson (University of Oxford); Dr Laurence Brown (University of Oxford)

References: 

see publications in http://iris.ucl.ac.uk/iris/browse/profile?upi=SCSTA01