Cognitive and behavioural neuroscience, Addiction, Impulsivity, Neuroimaging, Neuropharmacology
To investigate the neurobiological basis of individual vulnerability to drug addiction and associated behavioural traits.
Group leader - Dr Bianca Jupp
Dr Bianca Jupp’s research primarily investigates the neural mechanisms underlying addiction and addiction vulnerability with a particular emphasis on behavioural traits known to mediate risk for this disorder, such as impulsivity and cognitive flexibility.
Find out more about Dr Bianca Jupp
Affecting over 39 million people worldwide, drug addiction represents one of the leading causes of preventable death and disease in the developed world. Curiously, despite the prevalence of drug use within society only a relatively small proportion of users go on to develop addiction. The biological mechanisms underlying this differential vulnerability however, remain largely unknown. Importantly these mechanisms may represent potential targets for the development of therapeutics to treat, or indeed, prevent this chronic disease.
To investigate this, our work aims to elucidate the molecular and neural substrates of various behavioural traits co-expressed in individuals at risk for addiction, such as impulsivity, and determine how these in turn contribute to the emergence of addictive behaviour. This work predominantly utilises neuroimaging approaches (MRI and PET) combined with the more conventional molecular and pharmacological techniques in rodent models.
Impulsivity describes a tendency to make rash, risky and poorly thought through decisions or actions and is associated with a number of neuropsychiatric disorders including ADHD, suicide and drug addiction. Burgeoning evidence suggests these disorders are associated with alterations in neuroinflammatory processes in the brain. However, to date it is unknown whether impulsivity similarly shares this pathological hallmark.
The project will examine the inflammatory profile of the brain in rats, which naturally expresses high levels of impulsivity, and determine whether therapeutics targeting neuroinflammation may modulate the expression of this behaviour.
Impulsivity, a tendency to rash, risky decision-making is associated with increased risk for developing drug addiction. Like addiction, impulsivity is accompanied by deficits in striatal and midbrain dopamine D2 receptor function. It is unclear however how this pathological hallmark predisposes individuals to addiction. While recent evidence links reduced D2 receptor function to enhanced “bottom-up” motivational, drug-consummatory processes, there is also evidence linking D2 dysfunction to deficiencies in prefrontal cortical function as measured by fluoro-deoxy-glucose positron emission tomography (FDG-PET). Importantly, altered “top-down” prefrontal cortical function may influence an individual’s capacity for appropriate decision-making, which may in turn enhance an individual’s vulnerability to addiction. Finally, it is unclear whether the deficiencies in D2 function observed in impulsivity are limited to pre-synaptic auto-receptors on neurons, projecting from the midbrain to the striatum, or whether it also reflects effects on post-synaptic D2 receptors within this region.
This project will examine the effect of molecular knock-down of D2 receptors either within the midbrain or striatum on impulsivity, and function of the prefrontal cortex as measured by FDG-PET.
Selected Recent Publications
For full list of publications, visit Pubmed.
Google scholar profile.
- Jupp B, Jones JA, Dalley JW (2019). Modelling differential vulnerability to addiction in rodents: neurobiological mechanisms. In Substance Use Disorders: Handbook of Experimental Pharmacology, Michael Nader and Yasmin Hurd, Springer.
- Jupp B, Murray JE, Jordan ER, Xia J, Fluharty M, Shrestha S, Robbins TW, Dalley JW (2016). Social dominance in rats: effects on cocaine self-administration, novelty reactivity and dopamine receptor binding and content in the striatum. Psychopharmacology 233(4):579-89
- Belin-Rauscent A, Daniel ML, Puaud M, Jupp B, Sawiak S, Howett D, McKenzie C, Caprioli D, Besson M, Robbins TW, Everitt BJ, Dalley JW, Belin D (2016). From impulses to maladaptive actions: the insula is a neurobiological gate for the development of compulsive disorders. Molecular Psychiatry 21(4):491-9
- Caprioli D, Jupp B, Hong Y, Sawiak S, Ferrari V, Wharton L, Williamson D, McNabb C, Berry D, Aigbirhio F, Robbins T, Fryer T, Dalley JW, (2015). Dissociable rate dependent effects of oral methylphenidate on impulsivity and D2/3 receptor availability in the striatum. Journal of Neuroscience 35(9):3747-55.
- Jupp B, Dalley, JW (2014). Behavioral endophenotypes of drug addiction: etiological insights from neuroimaging studies. Neuropharmacology. 76:487-97.
- Jupp B, Dalley, JW (2014). Convergent pharmacological mechanisms in impulsivity and addiction: insights from rodent models. British Journal of Pharmacology 171(20):4729-66.