Effect of cocaine sensitization on cue-evoked reward seeking and dopamine release

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DESCRIPTION (provided by applicant): Environmental cues associated with reward can impact actions and decisions that involve responding for rewards. The influence of environmental cues on action selection is particularly relevant to addiction, in which we see a loss of behavioral control, and increases in habitual drug seeking behavior. Presentation of reward associated cues elicits dopamine (DA) release within the nucleus accumbens (NA), an effect that is believed to underlie increases in reward seeking. The incentive sensitization theory of addiction posits that repeated psychostimulant exposure sensitizes this system, allowing stimuli to more easily activate the DA system and enhance motivation. Thus, drug exposure should allow cues paired with reward to exert greater control over behavior, explaining the sensitive nature of cue-induced drug seeking behavior in addicted individuals. The first objective of the proposed experiments will be to determine, in rats, if cocaine sensitization potentiates cue- evoked reward responding and DA release in the NA and will provide me with training in fast-scan cyclic voltammetry and the Pavlovian-to-instrumental paradigm. The association of a cost with a large reward option can decrease its value and shift choice toward a smaller, less costly reward, and addicted individuals have been repeatedly shown to be more likely to discount larger, more costly rewards, than healthy controls. Interestingly, the presence or absence of reward-related cues appears to shift behavior towards different options. However, it is currently not clear how alterations in cue-evoked DA release, following cocaine sensitization, impacts the effects of cue presence or absence on choice preference. The second objective of the proposed experiments will therefore be to determine how cocaine induced sensitization impacts the effects of reward-associated cues on choice preference, in delay and effort discounting task. Fast-scan cyclic voltammetry will again be used to determine associated changes in dopamine levels within the brain, during cue presentation and choice preference. Impairments in cost-benefit decision making may contribute to addiction by driving behavior towards immediate rewards requiring less effort, such as those associated with drug use (euphoria, relief from withdrawal symptoms), over more effortful, but ultimately more beneficial, rewards associated with abstinence (e.g. - better health, employment, family relationships). Understanding the role of cues, as well as the role of dopamine, in responding for rewards, particularly when different reward-cost options are available, is important to our understanding of how drugs of abuse modify behavior and decision making, as well as for the development of treatment strategies.