Habit formation and the loss of control of an internal clock: inverse relationship between the level of baseline training and the clock-speed enhancing effects of methamphetamine

Introduction: Drugs that modulate the effective level of dopamine (DA) in cortico-striatal circuits have been shown to alter the perception of time in the seconds-to-minutes range. How this relationship changes as a function of repeated experience with the reinforcement contingencies and the gradual adaptation of the underlying neural circuits remains unclear. Materials and methods: The present study examined the clock-speed enhancing effects of methamphetamine (MAP 0.5 or 1.0 mg/kg, ip) in groups of rats that received different levels of baseline training (20, 60, or 120 sessions) on a 50-s peak-interval (PI) procedure before initial drug administration. Results: A curvilinear relationship was observed such that rats that received either minimal or intermediate levels of training (60 sessions or less) displayed dose- x training-related horizontal leftward shifts in their timing functions, suggesting that the speed of the internal clock was increased. In contrast, rats that had received an extended level of training (120 sessions or more) did not show this "classic" DA agonist curve-shift effect, but instead displayed a dose-dependent disruption of temporal control after MAP administration. A transition from DA-sensitive to DA-insensitive mechanisms is proposed to account for the loss of control of clock speed, as timing behaviors associated with the PI procedure gradually become learned habits through the strengthening of DA-glutamate connections. [PUBLICATION ABSTRACT]