Thursday, November 21, 2024
11/21/2024
Instead of asking “How is perceived time altered by drug administration?”, in order to better understand drug addiction, this proposal addresses the question in reverse, asking “How do temporal expectations directly influence the processes underlying addiction?”. A number of drug addiction models have identified different underlying processes that contribute to drug dependence, including magnified incentive motivation processes (‘wanting’, Robinson and Berridge,1993) dampened hedonic responsiveness ('liking', Koob and Le Moal 2001), and habitual drug seeking (Everitt, Dickinson et al. 2001). These models concur that drug-associated cues promote drug seeking. While it has been well established that the time between a conditioned cue and its predicted outcome moderates the magnitude and timing of conditioned behavior, addiction models essentially ignore the contribution of these implicit temporal expectations. The guiding hypothesis of the proposed project is that the time between drug cues and drug intake influences the magnitude and timing of the psychological and physiological processes that underlie addiction. Understanding the temporal dynamics of these addiction-related processes may be of critical importance to applied treatment options for substance addicted patients, for example, by optimizing “schedule reduction” treatment schedules to the temporal fluctuations in drug craving (Cinciripini, Lapitsky et al. 1995). Specifically, we hypothesize that drug ‘wanting’ induced by conditioned drug-associated stimuli will be maximal at the time that drug administration usually occurs, whereas drug ‘liking’ will be minimal at the time that drug administration usually occurs. We propose three aims to examine the temporal dynamics of motivation and hedonic evaluation in rodents trained to expect temporally predictable reinforcement (US) in response to Pavlovian conditioned cues (CS). In Aim 1, we will investigate whether hedonic evaluation is modulated by time, by using a negative anticipatory contrast paradigm which provides an assessment of changes in hedonic palatability as a function of expectation. We hypothesize that ‘liking’ will be diminished in a dynamic manner that reflects the expected time of a future reward. Such results would support our hypothesis that temporal expectations shape hedonic experience. In Aim 2, we will examine cue-induced ‘wanting’ using the Pavlovian-Instrumental Transfer paradigm. We predict that the temporally specific relations learned during the Pavlovian phase will be reflected in the strength of instrumental responding when the CS is presented (i.e., temporal transfer), thereby supporting the hypothesis that conditioned motivation can be temporally dynamic, rather than static. In Aim 3, we examine the role of temporal expectations on ‘wanting’ and ‘liking’ when an abused drug is the expected outcome (i.e., nicotine or ethanol). In addition, we will concurrently record heart rate and body temperature to evaluate whether compensatory opponent processes of physiological systems are impacted by the expected time of drug availability.
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