Targeting glucocorticoid receptors that promote resilience in the treatment of addiction

Bartlett, Selena, Holgate, Joan, Tarren, Josephine, Belmer, Arnauld, & Johnson, Luke R. (2015) Targeting glucocorticoid receptors that promote resilience in the treatment of addiction. In 25th Biennial Meeting of the International Society for Neurochemistry jointly with the 13th Meeting of the Asian-Pacific Society for Neurochemistry in conjunction with the 35th Meeting of the Australasian Neuroscience Society, 23-27 August 2015, Cairns, Australia.

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There is strong evidence to suggest that the combination of alcohol and chronic repetitive stress leads to long-lasting effects on brain function, specifically areas associated with stress, motivation and decision-making such as the amygdala, nucleus accumbens and prefrontal cortex. Alcohol and stress together facilitate the imprinting of long-lasting memories. The molecular mechanisms and circuits involved are being studied but are not fully understood. Current evidence suggests that corticosterone (animals) or cortisol (humans), in addition to direct transcriptional effects on the genome, can directly regulate pre- and postsynaptic synaptic transmission through membrane bound glucocorticoid receptors (GR). Indeed, corticosterone-sensitive synaptic receptors may be critical sites for stress regulation of synaptic responses. Direct modulation of synaptic transmission by corticosterone may contribute to the regulation of synaptic plasticity and memory during stress (Johnson et al., 2005; Prager et al., 2010). Specifically, previous data has shown that long term alcohol (1) increases the expression of NR2Bcontaining NMDA receptors at glutamate synapses, (2) changes receptor density, and (3) changes morphology of dendritic spines (Prendergast and Mulholland; 2012). During alcohol withdrawal these changes are associated with increased glucocorticoid signalling and increased neuronal excitability. It has therefore been proposed that these synapse changes lead to the anxiety and alcohol craving associated with withdrawal (Prendergast and Mulholland; 2012). My lab is targeting this receptor system and the amygdala in order to understand the effect of combining alcohol and stress on these pathways. Lastly, we are testing GR specific compounds as potential new medications to promote the development of resilience to developing addiction.

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ID Code: 88926
Item Type: Conference Item (Other)
Refereed: No
Additional Information: Abstract published in Journal of Neurochemistry, Volume 134, Issue Supplement S1, pages 35–36, August 2015
Keywords: Glucocorticoid, Receptors, Resilience, Addiction
DOI: 10.1111/jnc.13185
ISSN: 1471-4159
Divisions: Current > Schools > School of Clinical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 12 Oct 2015 00:23
Last Modified: 12 Oct 2015 00:23

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