Alcohol and striatal adaptation
Alcohol drinking and cigarette smoking are amongst the leading worldwide causes of preventable death and disease. Moreover, alcohol and tobacco are commonly co-abused and animal studies have implicated potential overlapping mechanisms of action in the brain.
(i) perform analogous RNA-Seq studies in human alcoholic brain compared to age-matched control brain.
(ii) characterise the molecular and electrophysiological consequences of chronic intermittent alcohol intake on cholinergic transmission in the rat striatum.
(iii) examine in rats how pharmacological manipulation of nicotinic and muscarinic M5 receptors, alone and in combination, impacts upon alcohol use / relapse.
In this regard both alcohol and tobacco impact central cholinergic systems and drugs acting at nicotinic receptors can regulate both drinking and smoking. Importantly, we have recently confirmed the functional relevance of lateral striatal M5 muscarinic receptors in regulating voluntary alcohol intake.
These novel findings allow us to hypothesise that plastic adaption of cholinergic signalling occurs following chronic intermittent alcohol in the lateral striatum.
Overall, this novel and innovative study will lead the field by characterising the molecular effects of chronic alcohol use in human caudate (medial striatum) vs putamen (lateral striatum); characterising the impact of alcohol on striatal cholinergic transmission and a parallel preclinical assessment of a potential novel therapeutic target, namely the muscarinic M5 receptor.
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