Exploring the basis of cognitive function and impulse control at a neural, neurochemical and molecular level using rodent analogues of human neuropsychological tests; emphasis on frontostriatal systems, goal-directed behaviour, serotonin, dopamine and noradrenaline.
Much of the progress in the medical field has been made through the development of animal models of illness. Although mental illnesses are fundamentally difficult to model in animals, it is possible to design cognitive behavioural tests for rats and other species which are very similar to the tests used clinically to identify cognitive dysfunction in psychiatric populations. We can then study how well animals perform these tests after different pharmacological or behavioural manipulations, and use that information to make testable predictions regarding the workings of the human brain.
When we propose to model impulsivity in a lab setting, we need to think about what the term "impulsivity" really means. Factor analysis of self-report questionnaires reveals that impulsivity is made up of a number of relatively independent dimensions which can be affected to different degrees in individuals with impulse control disorders (ICDs). By fractionating impulsivity into its component parts, it has proved possible to design specific behavioural tests which measure different types of impulsivity, and related processes, in rats. Research in both humans and animals indicate that these different forms are critically regulated by different brain regions and neurotransmitter systems. A better understanding of this biological regulation could stimulate the development of better treatments for ICDs, and explain why not all individuals respond to the same therapies.
Specific projects include:
Winstanley CA, LaPlant Q , Theobald DE , Green TA, Bachtell RK , Perrotti LI , DiLeone RJ, Russo SJ, Garth WJ , Self DW, Nestler EJ (2007) "DeltaFosB induction in orbitofrontal cortex mediates tolerance to cocaine-induced cognitive dysfunction." Journal of Neuroscience 27: 10497-507.
Winstanley CA, Eagle DM and Robbins TW (2006) “Behavioural models of impulsivity: translation between clinical and preclinical studies” Clinical Psychology Review (4):379-95.
Winstanley CA, Theobald DEH, Dalley JW, Cardinal RN and Robbins TW (2006) “Double dissociation between serotonergic and dopaminergic modulation of medial prefrontal and orbitofrontal cortex during a test of impulsive choice” Cerebral Cortex, 16: 106-14
Winstanley CA, Baunez C, Theobald DEH and Robbins TW (2005) “Lesions to the subthalamic nucleus decrease impulsive choice yet impair autoshaping in rats: the importance of the basal ganglia in Pavlovian conditioning and impulse control” European Journal of Neuroscience 11: 3107-16
Winstanley CA, Dalley, JW, Theobald DEH and Robbins TW (2005) “Interactions between serotonin and dopamine in the control of impulsive choice in rats: therapeutic implications for impulse control disorders” Neuropsychopharmacology 30: 669-82
Winstanley CA, Theobald DEH, Cardinal RN and Robbins TW (2004) “Contrasting roles of basolateral amygdala and orbitofrontal cortex in impulsive choice” Journal of Neuroscience 19: 4718-4722
PSYC 361 Motivation, PSYC 304 Brain and Behaviour