INTERVAL TIMING BEHAVIOR--ENSEMBLE RECORDING/STIMULANTS

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Previous work has demonstrated a relationship between the internal clock used for duration perception and reinforcement rate. As such, a full understanding of the changes in perceived event duration due to psychostimulant administration, as well as the mechanisms underlying these changes, are crucial to the formation of successful strategies of prevention and treatment of drug abuse. The current proposal seeks to understand the neural mechanisms underlying psychostimulant-induced perceptual changes in interval timing. This will be accomplished by simultaneous extracellular recording of multiple neurons, in multiple brain nuclei, in a rat on and off and off psychostimulants (e.g., methamphetamine and cocaine) while performing in a temporal-production task. Experiment 1 investigates the spatiotemporal patterns of neural firing during timing behavior within the substantia nigra pars compacta, caudate-putamen, and medial prefrontal cortex (areas believed to underlie duration perception). The changes in neural activity patterns, before and after stimulant administration, will be matched to observed behavioral changes. Experimetn 2 is designed to investigate the dynamic changes in the neural firing patterns during chronic stimulant administration. Previous work has demonstrated a specific pattern of changes in temporal perception during chronic stimulant administration which is qualitatively similar to descriptions of tolerance following withdrawal from chronic stimulants. Utilizing differing routes of chronic methamphetamine and cocaine administration: continuous vs. intermittent, the development of behavioral and pharmacodynamic sensitization an tolerance can be manipulated. Ensemble recording of the hypothesized timing circuit during this development will allow investigation of the underlying mechanisms causing these changes. Finding a specific relationship between changes in time perception and chronic stimulant-induced tolerance will implicate the use of treatment strategies designed to alter duration memory in order to counter the effects of these stimulant-induced changes in perceived time.