Phone: 604 822-4624
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Research in our laboratory addresses two separate issues in the field of behavioural neuroscience. The first concerns the role of brain nomoamines, in particular dopamine, in animal models of motivation and emotion. Through the use of psychopharmacological procedures, and more recently direct in vivomonitoring of changes in extracellular dopamine, the mesotelencephalic dopamine systems has been linked to incentive motivational stimuli that elicit preparatory responses. Significant changes in dopamine have been observed prior to and during sexual behaviour and feeding behaviour. Similar increases also accompany brain-stimulation reward and intravenous self-administration of cocaine. The specific techniques involved in the latter studies are in vivo electrochemistry and microdialysis.
Our second program of research is concerned with the relative contribution of separate neural circuits which project to the ventral striatum, to neural processes underlying learning and memory. Selective manipulations of different structures within these circuits with receptor-specific agonists/antagonists reveal separate roles for the prefrontal cortex, ventral subiculum and nucleus accumbens in spacially-mediated delayed memory tasks. Parallel electrophysiological neurochemical and neuropharmacological studies focus on the role of Long-Term Depression of synaptic activity in mediating cognition and memory within these neural circuits.
Brebner, K., Wong, T.P., Liu, L., Campsall, P., Gray, S., Phelps, L., Phillips, A.G., Wang., Y.T. Nucleus accumbens long-term depression and the expression of behavioural sensitization. Science, 310:1340-1343 (2005).
Phillips, A.G., Vacca, G., Ahn, S. A top-down perspective on dopamine, motivation and memory. Pharmacology Biochemistry and Behavior, 90(2):236-49 (2008).
Ge, Y., Dong, Z., Bagot, R.C., Howland, J.G., Phillips, A.G., Wong, T.P., Wang, Y.T. Hippocampal long-term depression is required for the consolidation of spatial memory. Proceedings of the National Academy of Sciences of the USA, 107(38):16697-16702 (2010).
Butts, K.A., Weinberg, J., Young, A.H., Phillips, A.G. Glucocorticoid receptors in the prefrontal cortex regulate stress-evoked dopamine efflux and aspects of executive function. Proceedings of the National Academy of Sciences of the USA, 108(45):18459-64 (2011).
Dalton, G.L., Wu, D.C., Wang, Y.T., Floresco, S.B., Phillips, A.G. NMDA GluN2A and GluN2B receptors play separate roles in the induction of LTP and LTD in the amygdala and in the acquisition and extinction of conditioned fear. Neuropharmacology, 62(2):797-806 (2011).
Lapish, C.C., Belardetti, F., Ashby, D.M., Ahn, S., Butts, K.A., So, K., Macrae, C.M., Hynd, J.J., Miller, J.J., Phillips, A.G. A preclinical assessment of D,L-govadine as a potential antipsychotic and cognitive enhancer. International Journal of Neuropsychopharmacology, 10:1-15 (2011).
St Onge, J.R., Ahn, S., Phillips, A.G., Floresco, S.B. Dynamic Fluctuations in Dopamine Efflux in the Prefrontal Cortex and Nucleus Accumbens during Risk-Based Decision Making. Journal of Neuroscience, 32(47):16880-91 (2012).