Characterisation of the galanin-3 receptor in drug-seeking behaviour

Submission note: A thesis submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy to the Department of Human Biosciences, Faculty of Health Sciences, La Trobe University, Bundoora.

The neuropeptide galanin has an important role in promoting alcohol consumption and general feeding behaviour. Galanin acts by binding to three receptor subtypes located within brain regions that play a key role in addiction. This thesis explores the role of galanin in alcohol-seeking behaviour with specific investigation into the galanin-3 receptor (GALR3) as a potential target for the treatment of alcohol abuse disorders. Studies outlined in this thesis are the first to demonstrate that treatment with the GALR3 antagonist, SNAP 37889, significantly reduced operant responding for alcohol and prevents cue-induced reinstatement of drug-seeking behaviour in rats. Chapters 3-5 describe autoradiographical binding studies carried out in the brains of alcohol-preferring (P) rats. These studies have identified specific regions where galanin may contribute to alcohol consumption. Given the influence of genetic background on the risk for alcoholism, Chapter 3 compared the brains of P and non-preferring (NP) rats and describes innate differences found in the galanin system, which may contribute to alcohol preference in these species. Chapter 4 broadly explored the role of galanin in reward-seeking and describes changes in galanin receptor density that occurred in regions of the brain following chronic consumption of ethanol, sucrose or saccharin. Chapter 5 describes significant changes in the brain of ethanol-naïve P rats, caused by acute and chronic treatment with the galanin-3 receptor antagonist, SNAP 37889. Behavioural experiments in Chapter 6 evaluated the use of GALR3 antagonists in reducing the motivational properties of alcohol and reducing relapse behaviour following abstinence. Taken together, data presented in this thesis indicate the involvement of galanin within subregions of the rat brain that are known to play a role in food consumption, rewardprocessing and addiction. In addition, results from these studies indicate the involvement of XXII GALR3 in motivational processes and relapse behaviours, which suggests that GALR3 antagonists may be of use in treating these aspects of alcoholism.