5 West 2.49c
Tel: +44 (0) 1225 38 4957
For more information on neuroscience research see our Neuroscience website.
Dr Chris Bailey
My research focuses on the neuronal changes caused by drugs of abuse, and how they relate to drug tolerance and addiction.
Morphine and related opiates such as heroin act by activating the µ-opioid receptor and are effective as analgesics, as well as being abused on the street. Following prolonged administration, tolerance occurs, whereby there is a need for escalating dose of that drug to maintain effect. This complicates pain-relief therapy as well as contributing to the social problems inherent in heroin addiction.
The mechanism(s) underlying opiate tolerance are poorly understood, but we have recently provided evidence that µ-opioid receptor desensitization may be a key process.
Interestingly, we have recently uncovered the fact that two different ligands at the µ-opioid receptor can cause receptor desensitization and internalization by entirely different intracellular signalling mechanisms. On-going research is designed to investigate the precise molecular mechanisms underlying mu-opioid receptor desensitization and internalization, and determine precisely how these events relate to tolerance using behavioural methods.
Synaptic Plasticity and Drug Addiction
Intake of drugs of abuse such as heroin, cocaine and ethanol can result in compulsive drug use. Synaptic plasticity is thought to underlie memory formation, and as compulsive drug use is a learned behaviour, current interest in the field of drug addiction is focusing on the role of synaptic plasticity in the responses to drugs of abuse. On-going research is designed to gain a better understanding of the molecular processes underlying synaptic plasticity caused by drugs of abuse in areas of the brain such as the ventral tegmental area, nucleus accumbens and frontal cortex, how these processes can be modulated, and their effects on drug addiction.
We use a combination of electrophysiological approaches and real-time cell imaging coupled with behavioural measures of reward, analgesia and respiratory depression.
Udakis, M., Wright, V., Wonnacott, S. and Bailey, C. P., 2016. Integration of inhibitory and excitatory effects of α7 nicotinic acetylcholine receptor activation in the prelimbic cortex regulates network activity and plasticity. Neuropharmacology, 105, pp. 618-629.
Hill, R., Lyndon, A., Withey, S., Roberts, J., Kershaw, Y., MacLachlan, J., Lingford-Hughes, A., Kelly, E., Bailey, C., Hickman, M. and Henderson, G., 2016. Ethanol reversal of tolerance to the respiratory depressant effects of morphine. Neuropsychopharmacology, 41 (3), pp. 762-773.
Lowe, J. D., Sanderson, H. S., Cooke, A. E., Ostovar, M., Tsisanova, E., Withey, S. L., Chavkin, C., Husbands, S. M., Kelly, E., Henderson, G. and Bailey, C. P., 2015. Role of G Protein-Coupled Receptor Kinases 2 and 3 in μ-Opioid Receptor Desensitization and Internalization. Molecular Pharmacology, 88 (2), pp. 347-356.
Almatroudi, A., Husbands, S. M., Bailey, C. P. and Bailey, S. J., 2015. Combined administration of buprenorphine and naltrexone produces antidepressant-like effects in mice. Journal of Psychopharmacology, 29 (7), pp. 812-821.
Bailey, S., Almatroudi, A. M. I., Bailey, C. and Husbands, S., 2015. The antidepressant-like effects of BU10119, a novel kappa opioid receptor antagonist, in the novelty-induced hypophagia task in mice. In: Society for Neuroscience 2015, 2015-10-17 - 2015-10-21, Chicago.
Bailey, C. P. and Husbands, S. M., 2014. Novel approaches for the treatment of psychostimulant and opioid abuse-focus on opioid receptor-based therapies. Expert Opinion on Drug Discovery, 9 (11), pp. 1333-1344.
Almatroudi, A., Husbands, S. M., Bailey, C. P. and Bailey, S. J., 2014. Combination Treatment With Buprenorphine/Naltrexone, A Functional Kappa Opioid Receptor Antagonist, Produces Antidepressant-Like Effects In Mice. Journal of Psychopharmacology, 28 (8), A101.
Cordery, S. F., Taverner, A., Ridzwan, I. E., Guy, R. H., Delgado-Charro, M. B., Husbands, S. M. and Bailey, C. P., 2014. A non-rewarding, non-aversive buprenorphine/naltrexone combination attenuates drug-primed reinstatement to cocaine and morphine in rats in a conditioned place preference paradigm. Addiction Biology, 19 (4), pp. 575-586.
Bailey, S., Almatroudi, A. M. I., Bailey, C. and Husbands, S., 2014. The antidepressant-like effects of combination buprenorphine/naltrexone in the novelty-induced hypophagia task in mice. In: Society for Neuroscience, 2014-11-15.
Llorente, J., Withey, S., Rivero, G., Cunningham, M., Cooke, A., Saxena, K., McPherson, J., Oldfield, S., Dewey, W.L., Bailey, C.P., Kelly, E. and Henderson, G., 2013. Ethanol reversal of cellular tolerance to morphine in rat locus coeruleus neurons. Molecular Pharmacology, 84 (2), pp. 252-260.
Hull, L.C., Gabra, B.H., Bailey, C.P., Henderson, G. and Dewey, W.L., 2013. Reversal of morphine analgesic tolerance by ethanol in the mouse. Journal of Pharmacology and Experimental Therapeutics, 345 (3), pp. 512-519.
Almatroudi, A., Husbands, S. M., Bailey, C. P. and Bailey, S. J., 2013. Establishing the combination of buprenorphine and naltrexone as a functional kappa opioid receptor antagonist in mice. Proceedings of the British Pharmacological Society
Llorente, J., Lowe, J. D., Sanderson, H. S., Tsisanova, E., Kelly, E., Henderson, G. and Bailey, C. P., 2012. μ-Opioid receptor desensitization: homologous or heterologous? European Journal of Neuroscience, 36 (12), pp. 3636-3642.
Rivero, G., Llorente, J., McPherson, J., Cooke, A., Mundell, S.J., McArdle, C.A., Rosethorne, E.M., Charlton, S.J., Krasel, C., Bailey, C.P., Henderson, G. and Kelly, E., 2012. Endomorphin-2: A biased agonist at the μ-opioid receptor. Molecular Pharmacology, 82 (2), pp. 178-188.
Lowe, J. D. and Bailey, C. P., 2011. Lack of agonist-induced desensitization of mu-opioid receptors located at nerve terminals. Pharmacological Reports, 63 (1), p. 235.
Zhang, X. L., Nicholls, R. E., Bailey, C. P., Upreti, C., Muller, W., Kandel, E. R. and Stanton, P. K., 2011. Role of group II metabotropic receptors in long-term plasticity of presynaptic vesicular release at glutamatergic synapses. Current Neuropharmacology, 9 (Supplement 1), p. 69.
Taverner, A., Cordery, S., Husbands, S. M., Guy, R. H., Delgado-Charro, B. M. and Bailey, C. P., 2011. Transdermal delivery of a buprenorphine/naltrexone combination for the treatment of polydrug abuse. Pharmacological Reports, 63 (1), p. 257.
McPherson, J., Rivero, G., Baptist, M., Llorente, J., Al-Sabah, S., Krasel, C., Dewey, W. L., Bailey, C. P., Rosethorne, E. M., Charlton, S. J., Henderson, G. and Kelly, E., 2010. μ-Opioid receptors: correlation of agonist efficacy for signalling with ability to activate internalization. Molecular Pharmacology, 78 (4), pp. 756-766.
Hull, L. C., Llorente, J., Gabra, B. H., Smith, F. L., Kelly, E., Bailey, C., Henderson, G. and Dewey, W. L., 2010. The effect of protein kinase C and G protein-coupled receptor kinase inhibition on tolerance induced by mu-opioid agonists of different efficacy. Journal of Pharmacology and Experimental Therapeutics, 332 (3), pp. 1127-1135.
Bailey, C. P., Oldfield, S., Llorente, J., Caunt, C. J., Teschemacher, A., Roberts, L., McArdle, C., Smith, F., Dewey, W., Kelly, E. and Henderson, G., 2009. Involvement of PKCα and G-protein-coupled receptor kinase 2 in agonist-selective desensitization of µ-opioid receptors in mature brain neurons. British Journal of Pharmacology, 158 (1), pp. 157-164.
Bailey, C. P., Llorente, J., Gabra, B. H., Smith, F. L., Dewey, W. L., Kelly, E. and Henderson, G., 2009. Role of protein kinase C and μ-opioid receptor (MOPr) desensitization in tolerance to morphine in rat locus coeruleus neurons. European Journal of Neuroscience, 29 (2), pp. 307-318.
Zamalloa, T., Bailey, C. P. and Pineda, J., 2009. Glutamate-induced post-activation inhibition of locus coeruleus neurons is mediated by AMPA/kainate receptors and sodium-dependent potassium currents. British Journal of Pharmacology, 156 (4), pp. 649-661.
Gabra, B. H., Bailey, C. P., Kelly, E., Smith, F. L., Henderson, G. and Dewey, W. L., 2008. Pre-treatment with a PKC or PKA inhibitor prevents the development of morphine tolerance but not physical dependence in mice. Brain Research, 1217, pp. 70-77.
Rodriguez-Martin, I., Braksator, E., Bailey, C. P., Goodchild, S., Marrion, N. V., Kelly, E. and Henderson, G., 2008. Methadone:Does it really have low efficacy at mu-opioid receptors? Neuroreport, 19 (5), pp. 589-593.
Kelly, E., Bailey, C. P. and Henderson, G., 2008. Agonist-selective mechanisms of GPCR desensitization. British Journal of Pharmacology, 153 (S1), S379-S388.
Oldfield, S., Braksator, E., Rodriguez-Martin, I., Bailey, C. P., Donaldson, L. F., Henderson, G. and Kelly, E., 2008. C-terminal splice variants of the μ-opioid receptor: existence, distribution and functional characteristics. Journal of Neurochemistry, 104 (4), pp. 937-945.
Hickman, M., Lingford-Hughes, A., Bailey, C., Macleod, J., Nutt, D. and Henderson, G., 2008. Does alcohol increase the risk of overdose death: the need for a translational approach. Addiction, 103 (7), pp. 1060-1062.
Bailey, C. P., Nicholls, R. E., Zhang, X. L., Zhou, Z. Y., Muller, W., Kandel, E. R. and Stanton, P. K., 2008. Gαi2 inhibition of adenylate cyclase regulates presynaptic activity and unmasks cGMP-dependent long-term depression at Schaffer collateral-CA1 hippocampal synapses. Learning and Memory, 15 (4), pp. 261-270.
Baptist, M., Braksator, E., Bailey, C., Kelly, E. and Henderson, G., 2008. Mu-opioid receptor internalisation:Studies using a pHluorin tag. Fundamental & Clinical Pharmacology, 22, p. 60.