The autophosphorylation of alpha Ca2+/calmodulin dependent protein kinase II (αCaMKII) is important for memory formation and is becoming increasingly implicated in the development of drug addiction. Previous work suggests that αCaMKII acts via the monoaminergic systems to facilitate the establishment of alcohol drinking behaviour. The present study aims to investigate whether αCaMKII autophosphorylation deficient αCaMKIIT286A mice show a difference in the rewarding properties of alcohol (2 g/kg, i.p.), as measured by conditioned place preference (CPP). We found that alcohol-induced CPP could be established at an accelerated rate in αCaMKIIT286A compared to wild type (WT) mice. Hyperactivity/hyper-arousal induced by the test environment was normalised by alcohol in the αCaMKIIT286A, but not WT mice. This effect could be conditioned to the test environment and may suggest enhanced negative reinforcing action of alcohol in αCaMKII autophosphorylation deficient mice.