Projects per year
Personal profile
Research interests
My research focuses on the neuronal changes caused by drugs of abuse, and how they relate to drug tolerance and addiction.
Opioid Tolerance
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 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 prefrontal cortex, how these processes can be modulated, and their effects on drug addiction.
Experimental Approaches
We use a combination of electrophysiological approaches and real-time cell imaging coupled with behavioural measures of reward, analgesia and respiratory depression.
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Network
Projects
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New tools for acute spatiotemporal control of GPCR signalling in vivo
Biotechnology and Biological Sciences Research Council
1/11/20 → 31/10/23
Project: Research council
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Kappa opioid receptors in opiate addiction
Bailey, C., Wonnacott, S., Heal, D. & Kuijer, E.
1/10/20 → 30/09/24
Project: UK industry
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Chronic effect of G protein-biased mu-opioid receptor agonists in the brain
1/10/19 → 30/09/23
Project: Research council
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Targeting nicotinic receptors to combat addiction by preventing relapse
Bailey, C., Wonnacott, S., Heal, D. & Coccia, G.
1/10/18 → 30/09/22
Project: UK industry
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Functional consequences of biased signalling at neuronal G protein-coupled receptors
1/10/17 → 30/09/21
Project: UK charity
Research Output
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A novel G protein-biased agonist at the δ opioid receptor with analgesic efficacy in models of chronic pain
Conibear, A. E., Asghar, J., Hill, R., Henderson, G., Borbely, E., Tekus, V., Helyes, Z., Palandri, J., Bailey, C. P., Starke, I., Williams, S., Kendall, D. & Kelly, E., 29 Feb 2020, In: Journal of Pharmacology and Experimental Therapeutics. 372, 2, p. 224-236 13 p.Research output: Contribution to journal › Article › peer-review
Open Access9 Citations (Scopus) -
A novel G protein-biased agonist at the μ opioid receptor induces substantial receptor desensitization through G protein-coupled receptor kinase
Groom, S., Blum, N. K., Conibear, A. E., Disney, A., Hill, R., Husbands, S. M., Li, Y., Toll, L., Kliewer, A., Schulz, S., Henderson, G., Kelly, E. & Bailey, C. P., 27 Nov 2020, In: British Journal of Pharmacology.Research output: Contribution to journal › Article › peer-review
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Morphine-induced respiratory depression is independent of β-arrestin2 signalling
Kliewer, A., Gillis, A., Hill, R., Schmidel, F., Bailey, C., Kelly, E., Henderson, G., Christie, M. J. & Schulz, S., 8 Jun 2020, In: British Journal of Pharmacology. 177, 13, p. 2923-2931 9 p.Research output: Contribution to journal › Article › peer-review
Open Access27 Citations (Scopus) -
Voltage modulates the effect of μ receptor activation in a ligand-dependent manner
Ruland, J. G., Kirchhofer, S. B., Klindert, S., Bailey, C. P. & Bünemann, M., 1 Aug 2020, In: British Journal of Pharmacology. 177, 15, p. 3489-3504 16 p.Research output: Contribution to journal › Article › peer-review
Open Access2 Citations (Scopus) -
Inhibition of alpha7 nicotinic receptors in the ventral hippocampus selectively attenuates reinstatement of morphine-conditioned place preference and associated changes in AMPA receptor binding
Wright, V. L., Georgiou, P., Bailey, A., Heal, D. J., Bailey, C. P. & Wonnacott, S., 3 Jun 2019, In: Addiction Biology. 24, 4, p. 590-603 14 p.Research output: Contribution to journal › Article › peer-review
Open Access7 Citations (Scopus)21 Downloads (Pure)