DOPAMINERGIC MECHANISMS OF INTERVAL TIMING & DRUG ABUSE

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DESCRIPTION (provided by applicant): The main goal of this proposal is to evaluate the impact of the characteristics of conditioned stimuli on the effects of abuse drugs in the context of a class of behaviors that was shown to accurately reflect the degree of intoxication: timing in the seconds-to-minutes range. While fundamental behavioral processes such as learning, rate calculation and decision making crucially rely on estimation and reproduction of time intervals, drugs of abuse result in distortions of time perception. Dopamine (DA) agonists (e.g., methamphetamine, AMP) result in behavior consistent with a speeding up of the internal clock, while DA antagonists (e.g., haloperidol, HAL) result in behavior consistent with a slowing of the clock. While there is the possibility that some reinforcing and addiction properties of DA agonists might be related to their effects on the internal clock, evidence suggests that DA might also serve attentional or predictive functions. It is therefore possible that besides clock-related effects, DA drugs might distort time perception indirectly by affecting the filtering or prediction of events. The experiments described in this proposal aim at dissociating the memory effects, clock-effects, and attentional effects of DA drugs on interval timing in the rat animal model, because DA neuropsychopharmacology is very similar in rats and humans. The main goals of the project are as follows: (1) To develop a set of procedures to evaluate the impact of the characteristics of conditioned stimuli on timing and memory for timing. By contrasting the timing of "empty" and "filled" intervals one can dissociate attentional from clock and memory effects. The modality bias will be examined by using auditory or visual timed cues. (2) To dissociate the attentional and clock effects of AMP and HAL by evaluating their effect on timing "empty" and "filled" intervals in rats. There are no studies of the effects of DA drugs on timing "empty" intervals. Dose response curves will be established for both AMP and HAL (three drug doses for each drug). (3) To dissociate the clock and attentional effects of AMP and HAL on interval timing, by studying the interruption of the timed interval by another event (gap). The experiments will dissociate the clock (shift left/right) and attentional (reset/stop) effects of AMP and HAL. There are no studies of the effects of DA drugs on memory for timing "empty" intervals or intervals with gaps. Together, the studies will inform current models of timing, time perception, and DA psychopharmacology. They will help elucidate the pharmacological basis of interval timing and understand the impact of the characteristics of the attentional cues on the distortions of time perception by drugs of abuse.