, 2009). These emerging views about the neural basis of drug addiction, and its potential

treatment, have moved well beyond Ku-0059436 purchase the original story offered by the DA hypothesis of “reward. After decades of research, and continuing theoretical developments, there has been a substantial conceptual restructuring in the field of DA research. Considerable evidence indicates that interference with mesolimbic DA transmission leaves fundamental aspects of the motivational and hedonic response to food intact (Berridge, 2007; Berridge and Kringelbach, 2008; Salamone et al., 2007). Behavioral measures such as progressive ratio break points and self-stimulation thresholds, which were once thought to be useful as markers of the “reward” or “hedonia” functions of DA, are now considered to reflect processes involving exertion of effort, perception of effort-related or opportunity costs, and decision making (Salamone, 2006; Hernandez et al., 2010). Several recent electrophysiology papers have demonstrated responsiveness of either presumed or identified ventral tegmental DA neurons to aversive stimuli (Anstrom and Woodward, 2005; Brischoux et al., 2009; Matsumoto and Hikosaka, 2009; Bromberg-Martin et al., 2010; Schultz, 2010; Lammel et al., 2011). Many investigators now emphasize the involvement of mesolimbic and nigrostriatal DA in reinforcement learning or habit formation (Wise, 2004; Yin

et al., 2008; Belin et al., 2009), rather than hedonia per se. These trends have all contributed to

a dramatic rewriting of the story of dopaminergic involvement in motivation. The term motivation refers Z-VAD-FMK mw to a construct that is widely used in psychology, psychiatry, and neuroscience. As is the case with many psychological concepts, the discussion of motivation ADP ribosylation factor had its origins in philosophy. In describing causal factors that control behavior, the German philosopher Schopenhauer (1999) discussed the concept of motivation in relation to the way that organisms must be in a position to “choose, seize, and even seek out the means of satisfaction.” Motivation also was a vital area of interest during the initial development of psychology. Early scientific psychologists, including Wundt and James, included motivation as a subject in their textbooks. Neobehaviorists such as Hull and Spence frequently employed motivational concepts such as incentive and drive. Young (1961) defined motivation as “the process of arousing actions, sustaining the activity in progress, and regulating the pattern of activity.” According to a more recent definition, motivation is “the set of processes through which organisms regulate the probability, proximity and availability of stimuli” (Salamone, 1992). Generally speaking, the modern psychological construct of motivation refers to the behaviorally-relevant processes that enable organisms to regulate both their external and internal environment (Salamone, 2010).