Item Details

abstract

Methylphenidate (MPH), the active compound in the medication Ritalin, is commonly diverted for off-label use. It is abused at high rates in both the adolescent and adult population; however, until recently, the neurochemical effects of MPH abuse had not been explored in depth. Pharmacologically MPH is a dopamine transporter (DAT) blocker with the same mechanism of action and equivalent potency at the DAT as cocaine. Although MPH is categorized as a DAT blocker, its pharmacological actions are distinct from both blockers and releasers in regards to both its acute effects and the compensatory alterations associated with self-administration of the compound. This work has elucidated the neurochemical consequences of MPH self-administration, whereby MPH administration by a number of paradigms results in consistent neurochemical adaptations characterized by increased maximal rates of uptake (Vmax), increased DAT levels, increased evoked dopamine (DA) release, and an increased potency to inhibit the DAT for MPH and releasers, but not blockers. These changes are opposite from the documented changes that occur following cocaine self-administration, further suggesting that the neurochemical consequences of MPH are unique, and cannot be predicted based on previous literature of compounds of the same psychostimulant class, such as cocaine. The changes directly at the DAT following MPH self-administration are consistent with microdialysis and behavioral analysis that demonstrate increased MPH and amphetamine (AMPH)-induced DA overflow, but not cocaine, and increased reinforcing efficacy of AMPH and MPH, but not cocaine. The increases in the reinforcing efficacy of MPH and releasers such as AMPH, suggests that these compounds may having significant abuse liability following MPH abuse in the adolescent and adult populations.

subject

amphetamine

cocaine

Dopamine

methylphenidate

Self-administration

Voltammetry

contributor

Calipari, Erin Sue (author)

Jones, Sara R (committee chair)

Martin, Thomas J (committee member)

Chen, Rong (committee member)

McCool, Brian A (committee member)

Childers, Steven (committee member)

date

2014-01-15T09:35:41Z (accessioned)

2015-01-15T09:30:09Z (available)

2013 (issued)

degree

Physiology and Pharmacology (discipline)

embargo

2015-01-15 (terms)

identifier

http://hdl.handle.net/10339/39143 (uri)

language

en (iso)

publisher

Wake Forest University

title

UNIQUE PHARMACODYNAMIC PROFILE OF METHYLPHENIDATE: SELF-ADMINISTRATION-INDUCED DOPAMINE SYSTEM ALTERATIONS

type

Dissertation