Brain reward in the absence of alpha-synuclein

Alpha-synuclein has been implicated in the pathophysiology of Parkinson's disease. Recent studies revealed its role as a negative regulator of dopamine release in the nigrostriatal dopaminergic system. Alpha-synuclein may, however, play a more universal role in dopaminergic neurotransmission. It may represent an endogenous modulator in the mesolimbic dopaminergic system, and be involved in brain reward. We show here that the absence of alpha-synuclein resulting from spontaneous mutation in a subline of C57BL/6J mice greatly increased the rate of operant behavior during intracranial self-stimulation. The present work demonstrates that a lack of alpha-synuclein sensitized the brain reward system, implying that the levels of alpha-synuclein expression may predispose an individual to drug abuse or to a number of psychiatric diseases.