Research Project
8180102
DESCRIPTION (provided by applicant): The perception of time allows individuals to adapt to the temporal regularities of environmental events. It also plays a direct role in the choices we make. Delay discounting refers to the decrease in subjective value of a potential commodity (e.g., money, drugs, food) as a function of the expected delay until acquisition of that commodity, and numerous experiments have demonstrated "irrational" preference for the receipt of a small reward at a shorter delay over a larger reward at a longer delay. The rate of discounting has been shown to differ in individuals with substance abuse problems, and is thought to contribute to the short-sighted choice to take drugs. Importantly, changes in discounting rate can be understood as resulting from changes in temporal expectation, as a consequence of drug-induced alterations in temporal perception and temporal memory. Specifically, it has been shown that a number of abused drugs, including both psychostimulants and hallucinogenics, alter the perception of time. The global hypothesis underlying the proposed project is that memories associated with drug-present states are combined with drug-free memories when generating temporal expectations. These synthesized temporal expectations would then lead to alterations in anticipated value of possible choices (due to their impact on discounting), and may contribute to "impulsive" behaviors such as drug use. We have recently reported that rats trained with two component cues that each indicate food availability after a different interval has elapsed (e.g., tone = 10 sec and light = 20 sec) will demonstrate that they expect food at the average of these times (15s) when presented with the simultaneous compound cue (tone + light). We refer to this phenomenon as the synthesis of incongruent temporal information (SITI). Of particular relevance to the present project, we have also recently demonstrated that temporal memory synthesis can occur across drug states. Specifically, rats trained to expect food availability at 10s following saline adminstration, but 20s following amphetamine administration (0.5 mg/kg) will demonstrate temporal expectancy at 15s when tested, without feedback, following an intermediate dose of amphetamine (0.25 mg/kg). These data indicate that the memories associated with different drug states can be combined at retrieval to generate temporal expectancies that are maladaptive. Numerous questions remain about the nature of temporal memory synthesis across drug-states, as well as the conditions that promote SITI in drug naove subjects. The present application seeks to investigate the synthesis of drug state-associated temporal memories (Aim 1), investigate conditions related to incentive value that appear to moderate the incidence of SITI (Aim 2), develop procedures allowing an investigation of SITI in preference/choice (Aim 3), and investigate a novel hypothesis related to altered expectation due to drug-induced bias in temporal memory sampling. The work proposed here has significant potential to increase our understanding of the temporal expectations resulting from drug use that may influencing choice. PUBLIC HEALTH RELEVANCE: Temporal expectations are at the heart of delay discounting (the decrease in anticipated value of a commodity as a function of the expected delay until its receipt), and both temporal perception and the rate of delay discounting have been shown to be altered following acute and chronic drug use. We have shown that temporal memories formed during drug use can be averaged with temporal memories formed in drug-free states, and hypothesize that these combinatorial, maladaptive expectations will impact choice via their influence on anticipated value. The current project examines temporal memory synthesis across drug states, and the involvement of memory synthesis in choice behavior.
