Drug addiction is a disease with a devastating emotional and economic impact on society, which in turn has stimulated research that seeks to identify the neural mechanisms involved with addiction. Many lines of evidence suggest that drug addiction alters the motivation to pursue drugs. In particular, drug-related cues can promote motivated drug seeking through activation of the mesocorticolimbic dopamine system. However, little is known regarding how reinforcer-associated cues affect dopamine release in the nucleus accumbens (NAcc) in behaviors specifically examining motivation. Identifying the role of dopamine release to cues associated with reinforcer availability during motivated behaviors will improve our understanding of the neurochemical signals involved with motivation, and will also highlight specific dopamine release patterns that when blocked, could potentially attenuate how drug-related cues promote drug seeking. Motivation is often assessed in operant tasks that utilize progressive ratio (PR) reinforcement schedules. During PR reinforcement schedules, the net value of the reinforcer is diminished as the operant requirement to obtain a reinforcer increases on subsequent trials until operant responding ceases, which is the 'break- point'and is a measure of motivational effort one will expend to obtain a reinforcer. While dopamine release in the NAcc is involved with motivated operant output, surprisingly little is known regarding the temporal release patterns of dopamine during motivated behaviors. Phasic (sub-second) dopamine release in the NAcc precedes the initiation of goal-directed actions, which suggests that phasic dopamine release is involved with motivated behaviors. However, it is unknown how dopamine is released to cues associated with reinforcer availability in behavioral paradigms explicitly assessing motivation. In this regard, this proposal addresses this experimental question by utilizing voltammetry to determine the role of phasic, sub- second dopamine release in the NAcc to cues predicting reinforcer availability in rats during an operant task with a PR reinforcement schedule for either natural reinforcers (Aim 1) or drugs of abuse (Aim 2). A critical component of drug addiction is an enhanced motivation to purse drugs, which involves the actions of dopamine, although it is unknown how dopamine is released during behaviors specifically examining motivation. This proposal examines the role of sub-second dopamine release in the motivated pursuit of both natural (food) and drug (cocaine) reinforcers, which will enhance our understanding of the neurochemical signals involved with motivated behaviors, and will also highlight specific dopamine release patterns that when blocked, could reduce the motivation to pursue drugs.
