title: Long-term daily access to alcohol alters dopamine-related synthesis and signaling proteins in the rat striatum.
abstract: Chronic alcohol exposure can adversely affect neuronal morphology, synaptic architecture and associated neuroplasticity. However, the effects of moderate levels of long-term alcohol intake on the brain are a matter of debate. The current study used 2-DE (two-dimensional gel electrophoresis) proteomics to examine proteomic changes in the striatum of male Wistar rats after 8 months of continuous access to a standard off-the-shelf beer in their home cages. Alcohol intake under group-housed conditions during this time was around 3-4 g/kg/day, a level below that known to induce physical dependence in rats. After 8 months of access rats were euthanased and 2-DE proteomic analysis of the striatum was conducted. A total of 28 striatal proteins were significantly altered in the beer drinking rats relative to controls. Strikingly, many of these were dopamine (DA)-related proteins, including tyrosine hydroxylase (an enzyme of DA biosynthesis), pyridoxal phosphate phosphatase (a co-enzyme in DA biosynthesis), DA and cAMP regulating phosphoprotein (a regulator of DA receptors and transporters), protein phosphatase 1 (a signaling protein) and nitric oxide synthase (which modulates DA uptake). Selected protein expression changes were verified using Western blotting. We conclude that long-term moderate alcohol consumption is associated with substantial alterations in the rat striatal proteome, particularly with regard to dopaminergic signaling pathways. This provides potentially important evidence of major neuroadaptations in dopamine systems with daily alcohol consumption at relatively modest levels.
authors.affiliation: Psychopharmacology and Proteomics Laboratory, School of Psychology, The University of Sydney, NSW 2006, Australia. kabul@psych.usyd.edu.au
authors.forename: Mohammed Abul
authors.initials: MA
authors.lastname: Kashem
authors.forename: Selina
authors.initials: S
authors.lastname: Ahmed
authors.forename: Ranjana
authors.initials: R
authors.lastname: Sarker
authors.forename: Eakhlas U
authors.initials: EU
authors.lastname: Ahmed
authors.forename: Garth A
authors.initials: GA
authors.lastname: Hargreaves
authors.forename: Iain S
authors.initials: IS
authors.lastname: McGregor
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D001515:Beer / Q000009:adverse effects; D015153:Blotting, Western; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D013058:Mass Spectrometry; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D018377:Neurotransmitter Agents / Q000096:biosynthesis* / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D015290:Second Messenger Systems; D013997:Time Factors
chemical_list: D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D000431:Ethanol; D000242:Cyclic AMP; D004298:Dopamine