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These are the NMDA, GABA<jats:sub>A<\/jats:sub>, glycine, 5\u2010hydroxytryptamine 3 (serotonin) and nicotinic ACh receptors as well as L\u2010type Ca<jats:sup>2+<\/jats:sup>channels and G\u2010protein\u2010activated inwardly rectifying K<jats:sup>+<\/jats:sup>channels. Following this first hit of alcohol on specific targets in the brain, a second wave of indirect effects on a variety of neurotransmitter\/neuropeptide systems is initiated that leads subsequently to the typical acute behavioural effects of alcohol, ranging from disinhibition to sedation and even hypnosis, with increasing concentrations of alcohol. Besides these acute pharmacodynamic aspects of alcohol, we discuss the neurochemical substrates that are involved in the initiation and maintenance phase of an alcohol drinking behaviour. Finally, addictive behaviour towards alcohol as measured by alcohol\u2010seeking and relapse behaviour is reviewed in the context of specific neurotransmitter\/neuropeptide systems and their signalling pathways. The activity of the mesolimbic dopaminergic system plays a crucial role during the initiation phase of alcohol consumption. Following long\u2010term, chronic alcohol consumption virtually all brain neurotransmission seems to be affected, making it difficult to define which of the systems contributes the most to the transition from controlled to compulsive alcohol use. However, compulsive alcohol drinking is characterized by a decrease in the function of the reward neurocircuitry and a recruitment of antireward\/stress mechanisms comes into place, with a hypertrophic corticotropin\u2010releasing factor system and a hyperfunctional glutamatergic system being the most important ones.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2008)<jats:bold>154<\/jats:bold>, 299\u2013315; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"fn1\">fn1<\/jats:ext-link>; published online 3 March 2008<\/jats:p>","DOI":"10.1038\/bjp.2008.30","type":"journal-article","created":{"date-parts":[[2008,3,3]],"date-time":"2008-03-03T12:08:25Z","timestamp":1204546105000},"page":"299-315","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":463,"title":["Neuropharmacology of alcohol 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