Project Title: Sex-dependent role of dopamine D3 receptors in the individual vulnerability to develop compulsive drug seeking and taking behaviour: preclinical investigations using a novel highly selective antagonist
Supervisor: Professor David Belin
Department/Institute: Physiology, Development & Neuroscience (PDN)
Industrial Partner: Shionogi
Project details:
The opioid epidemic that has been claiming the lives of over half a million people in the US in the past decade is reaching the UK. There are still no effective treatments for addiction to opiate and other drugs such as cocaine and alcohol, thereby limiting our ability to help those who suffer from this debilitating psychiatric disorder, in part due to our lack of understanding of the cellular mechanisms mediating the transition from controlled to compulsive drug seeking and taking behaviour, the hallmark of substance use disorder. Among candidate mechanisms, those downstream of the dopamine D3 receptor, whose expression is profoundly exacerbated by exposure to addictive drugs, have long stood out. However, the role of this receptor in compulsive drug-seeking behaviour has never been determined due to the lack of appropriate procedures in non-human species. Capitalising on a novel animal model of compulsive heroin-seeking habits developed by the Belin lab, a new multi-million-pound partnership with Shionogi has recently been launched to test, among others, the therapeutic potential, and the associated neural signature, of a new highly selective dopamine D3 receptor on drug-seeking habits, compulsive drug seeking and escalation of drug self-administration in male and female rats. This programme of research at the interface of Behavioural neuroscience, neuropharmacology and molecular biology will provide a unique opportunity for a PhD student to acquire a deep knowledge of the psychological and neural basis of substance use disorders while also acquiring a wide range of experimental skills in a very supportive environment.
The industrial partner is one of the few Big Pharma laboratories left investing in fundamental research in neuroscience and pursuing the development of novel treatments for CNS disorders. It has long been interested in expanding their drug discovery strategy to drug addiction. Shionogi has become a primary industrial partner of the Cambridge landscape and is very active in its collaboration with the Cambridge Neuroscience Community. Over the past five years, Shionogi has supported a new line of research into the role of peripheral mu opiate receptors in the behavioural effects of opiates in the context of a BBSRC-ICase studentship with the Belin that has proven very successful, thereby being a testament to the commitment of Shionogi to support research in the field of substance use disorders.
Applicants will be expected to have extensive experience with chronic intravenous self-administration procedures in rats.
Further information on the Cambridge Bioscience DTP PhD programme can be found at this link: https://bbsrcdtp.lifesci.cam.ac.uk/bbsrc-dtp-programme/icase-studentships. Full details of the University's entrance requirements and scholarships are specified in the following link: https://www.postgraduate.study.cam.ac.uk/.