Rose Chesworth
Florey Neuroscience Institute
Ian Scott PhD Scholarship
Mental Health 2011
Rose completed her Bachelor of Psychology with Honours in 2007 at the University of Sydney. She then worked as a research assistant at Neuroscience Research Australia, examining interactions between the schizophrenia candidate gene Neuregulin 1 and environmental factors (e.g. drug use, stress) which precipitate the disorder. During this time she published two first author and three second author papers.
SUMMARY OF PROJECT:
The role of the metabotropic glutamate 5 and adenosine 2A receptors in methamphetamine addiction
Methamphetamine (METH) is a highly addictive stimulant drug with no effective pharmaceutical treatments. Recent research suggests a role for two brain receptors in behavioural and cortical processes for drugs of abuse: the metabotropic glutamate 5 (mGlu5) and adenosine 2A (A2A) receptors. This project aims to investigate the involvement of the mGlu5 and A2A receptors in behavioural and cortical processes relevant to METH addiction. Knockout (KO) mice (i.e. mice which lack these receptors) are being used for this purpose.
KO mice for the mGlu5 receptor have been tested in two behavioural paradigms relevant to drug-seeking behaviour. The first paradigm - conditioned place preference (CPP) - assessed the reward value of a drug-paired environment. In this, mGlu5 KO mice demonstrated a normal reward value for METH, suggesting this receptor is not critical for the initial rewarding effects of the drug. However, following the devaluation of the METH-paired environment (by no longer pairing it with drug reward) and the re-administration of METH (akin to an abstinent addict relapsing) mGlu5 KO mice did not display relapse-like behaviour; suggesting the possible involvment of this receptor in primed-relapse to METH seeking.
The second paradigm assessed drug-seeking behaviour through an operant self-administration paradigm. Mice were trained to press a lever to self-administer METH under different schedules of reinforcement (e.g. fixed ratio 1: one lever press provides one infusion of METH). mGlu5 KO mice learned to self-administer METH under different reinforcement schedules, suggesting no alteration to the reinforcing value of this drug, similar to the findings from the CPP paradigm. Relapse-like behaviour in mGlu5 KO mice is currently being assessed.
Molecular biology techniques are being employed to identify the localisation and expression of these receptors in the brain in response to METH-seeking. Through this we can determine the neural locations involved in the modulation of drug-seeking behaviours by these receptors. Optimisation of these methods is currently underway