Methylphenidate enhancement of early stage sensory processing

Drexel University, Philadelphia PA

Investigators

Linked publications, trials & patents

Abstract

DESCRIPTION (provided by applicant): Methylphenidate (MPH) is a psychostimulant routinely prescribed for treatment of attention deficit hyperactivity disorder (ADHD). Illicit use f MPH by non-ADHD individuals for performance enhancement is increasing in prevalence, raising significant health and ethical concerns. MPH is an amphetamine derivative that blocks the reuptake of catecholamine neurotransmitters, i.e. dopamine and norephinephrine (NE). Although much work has focused on the reinforcing effects and abuse liability associated with illicit use of MPH, we have limited understanding of the underlying mechanisms contributing to performance enhancement. MPH has been demonstrated to alter sensory evoked responsiveness in various cortical and thalamic sensory circuits, and we propose that augmentation of sensory signal processing is a component of psychostimulant-induced performance enhancement. The LC-NE system has long been associated with regulation of behavioral state and state-dependent processing of sensory information. Likewise, sensory processing is an essential component of both executive function and motor performance. As such, we propose that psychostimulant- mediated enhancement of NE neurotransmission within sensory circuits leads to augmentation of sensory signal processing and subsequent enhanced performance in a sensory signal detection task. The proposed studies will rely on multi-channel, multi-neuron recording and behavioral assays to investigate NE-receptor mediated mechanisms underlying psychostimulant-induced alterations in sensory processing and performance enhancement. We have previously shown that MPH enhances the responsiveness of individual cells to stimulus-driven inputs in the visual thalamus of the anesthetized rat. The first aim is to translate these findings into waking animals engaged in the performance of a visual detection task. The second and third aims are to identify the NE-receptor mechanisms that underlie the maintenance and facilitation of stimulus-driven light evoked activity within the visual thalamus during performance. The proposed research will investigate psychostimulant-induced augmentation of early-stage sensory signal processing as a potential core feature of performance enhancement in intact, behaving animals. The results are expected to provide key insight towards understanding the desirability of psychostimulants as performance enhancing compounds.