个人简介

I completed my PhD at the University of Queensland, Brisbane, Australia in 2000. The focus of this work was to identify parts of the brain that controlled neuroendocrine responses to different forms of stress. This work showed that different categories of stress - psychological or physiological (e.g. infection) - elicit distinct cellular activity "footprints" within the amygdala and sub-populations of catecholamine cells within the brainstem. This finding was because the consensus at the time was that these brain regions responded homogenously to stress irrespective of the 'category' or nature of the stimulus. At the end of my PhD I was awarded a CJ Martin fellowship from the NHMRC that allowed me to travel to the United States to undertake post-doctoral training at The Scripps Research Institute in California, San Diego. My post-doctoral research at The Scripps Research Institute contributed to the understanding of the neural pathways that control reinstatement of alcohol relapse. In articles published in the journal Biological Psychiatry and Journal of Neuroscience, I showed that the pattern of neural activity elicited by stimuli conditioned to predict the availability of alcohol, a factor linked to increased relapse risk in humans, is similar to the patterns produced by stimuli paired with the availability of other commonly abused drugs such as cocaine or nicotine. Additionally, we demonstrated how existing neuropharmacological treatments for alcoholism such as naltrexone, or newer agents that show promise in the treatment of addiction such as agonists for group II/III metabotropic glutamate (mGlu2/3) receptors, also modulate these patterns. We also showed that mGlu2/3 receptor agonists, which appear to have an anxiolytic profile, are effective in suppressing reinstatement (or relapse) elicited by stress - an important trigger for relapse in humans. At Scripps I also demonstrated that hypothalamic peptide systems, better known for their role in feeding behaviour, may be important neurotransmitters in the brain circuitry that trigger alcohol seeking behaviour. After returning to Australia, I established my own laboratory in the Discipline of Anatomy, School of Biomedical Sciences and Pharmacy, University of Newcastle to investigate the role of these hypothalamic peptides in driving drug-seeking and relapse-like behaviour. I received an NHMRC grant in to commence this work. My laboratory therefore focuses on the brain pathways that are involved in addiction and stress.

研究领域

Anatomy

Relapse to drug taking is considered the most significant obstacle to the successful treatment of addiction. Although much progress has been made in identifying individual brain regions that elicit drug-seeking behaviour and subsequently relapse, there are presently very few effectively pharmaceutical or indeed behavioural therapy strategies available to treat this disease. My research interests concern the following key issues: 1.Understanding the neuroanatomical and pharmacological interactions between key components of brain circuitry thought to be responsible for provoking drug relapse. 2.Determining the role of the neuropeptides (orexin/hypocretin and CART) recently found to be powerful modulators of drug-seeking and relapse. 3.Elucidating the cellular and molecular neuroadaptations that promotes long-term relapse vulnerability. 4.Determining the neurobiological basis for why some individuals become addicted and show greater vulnerability to drug relapse than others.

近期论文

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2015 Quinn RK, Brown AL, Goldie BJ, Levi EM, Dickson PW, Smith DW, et al., 'Distinct miRNA expression in dorsal striatal subregions is associated with risk for addiction in rats', Translational Psychiatry, 5 (2015) [C1] 2015 Campbell EJ, Watters SM, Zouikr I, Hodgson DM, Dayas CV, 'Recruitment of hypothalamic orexin neurons after formalin injections in adult male rats exposed to a neonatal immune challenge', Frontiers in Neuroscience, 9 (2015) [C1] 2015 Parkinson GM, Dayas CV, Smith DW, 'Age-related gene expression changes in substantia nigra dopamine neurons of the rat.', Mech Ageing Dev, 149 41-49 (2015) [C1] 2014 James MH, Quinn RK, Ong LK, Levi EM, Charnley JL, Smith DW, et al., 'mTORC1 inhibition in the nucleus accumbens 'protects' against the expression of drug seeking and 'relapse' and is associated with reductions in GluA1 AMPAR and CAMKIIa levels.', Neuropsychopharmacology, 39 1694-1702 (2014) [C1] 2014 Goldie BJ, Dun MD, Lin M, Smith ND, Verrills NM, Dayas CV, Cairns MJ, 'Activity-associated miRNA are packaged in Map1b-enriched exosomes released from depolarized neurons.', Nucleic Acids Research, 42 9195-9208 (2014) [C1] 2014 Parkinson GM, Dayas CV, Smith DW, 'Increased mitochondrial DNA deletions in substantia nigra dopamine neurons of the aged rat.', Current aging science, 7 155-160 (2014) [C2] 2014 Zouikr I, James MH, Campbell EJ, Clifton VL, Beagley KW, Dayas CV, Hodgson DM, 'Altered formalin-induced pain and fos induction in the periaqueductal grey of preadolescent rats following neonatal LPS exposure', PLoS ONE, 9 (2014) [C1] 2014 Yeoh JW, Campbell EJ, James MH, Graham BA, Dayas CV, 'Orexin antagonists for neuropsychiatric disease: progress and potential pitfalls.', Front Neurosci, 8 36 (2014) [C1] 2014 Yeoh JW, James MH, Graham BA, Dayas CV, 'Electrophysiological characteristics of paraventricular thalamic (PVT) neurons in response to cocaine and cocaine- and amphetamine-regulated transcript (CART)', FRONTIERS IN BEHAVIORAL NEUROSCIENCE, 8 (2014) [C1] 2014 James MH, Campbell EJ, Walker FR, Smith DW, Richardson HN, Hodgson DM, Dayas CV, 'Exercise reverses the effects of early life stress on orexin cell reactivity in male but not female rats', Frontiers in Behavioral Neuroscience, 8 (2014) [C1] 2013 James MH, Dayas CV, 'What about me ...? The PVT: a role for the paraventricular thalamus (PVT) in drug-seeking behavior', FRONTIERS IN BEHAVIORAL NEUROSCIENCE, 7 (2013) [C3] 2013 Cahif A, Parkinson GM, Dayas CV, Smith DW, 'Characterisation of mitochondrial DNA deletions by long-PCR in central nervous system regions of young, middle- and old-aged rats.', Current Aging Science, 6 232-238 (2013) [C1] 2013 Brown AL, Day TA, Dayas CV, Smith DW, 'Purity and Enrichment of Laser-Microdissected Midbrain Dopamine Neurons', BIOMED RESEARCH INTERNATIONAL, (2013) [C1] 2012 James MH, Yeoh JW, Graham B, Dayas C, 'Insights for Developing Pharmacological Treatments for Psychostimulant Relapse Targeting Hypothalamic Peptide Systems.', Journal of Addiction Research and Therapy, 01 1-14 (2012) 2012 Yeoh JW, James MH, Jobling P, Bains JS, Graham BA, Dayas CV, 'Cocaine potentiates excitatory drive in the perifornical/lateral hypothalamus', Journal of Physiology, 590 3677-3689 (2012) [C1] 2012 Dayas CV, Smith DW, Dunkley PR, 'An emerging role for the mammalian Target of Rapamycin (mTOR) in 'pathological' protein translation: Relevance to cocaine addiction', Frontiers in Pharmacology, 3 1-12 (2012) [C1] 2011 James MH, Charnley JL, Flynn JR, Smith DW, Dayas CV, 'Propensity to 'relapse' following exposure to cocaine cues is associated with the recruitment of specific thalamic and epithalamic nuclei', Neuroscience, 199 235-242 (2011) [C1] 2011 James MH, Charnley JL, Levi EM, Jones E, Yeoh JW, Smith DW, Dayas CV, 'Orexin-1 receptor signalling within the ventral tegmental area, but not the paraventricular thalamus, is critical to regulating cue-induced reinstatement of cocaine-seeking', International Journal of Neuropsychopharmacology, 14 684-690 (2011) [C1] 2011 Brown AL, Flynn JR, Smith DW, Dayas CV, 'Down-regulated striatal gene expression for synaptic plasticity-associated proteins in addiction and relapse vulnerable animals', International Journal of Neuropsychopharmacology, 14 1099-1110 (2011) [C1] 2010 James MH, Charnley JL, Jones E, Levi E, Yeoh JW, Flynn JR, et al., 'Cocaine- and amphetamine-regulated transcript (CART) signaling within the paraventricular thalamus modulates cocaine-seeking behaviour', Plos One, 5 e12980 (2010) [C1]