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Title: Relationship between dopamine transporter occupancy and methylphenidate induced high in humans

Abstract

The inhibition of the dopamine transporter (DAT) by cocaine has been shown to be indispensable for its reinforcing properties. The development of drugs that inibit the DAT has become a major target to prevent cocaine`s effects. However prevention of the {open_quotes}high{close_quotes} by DAT inhibitors has never been demonstrated. This study evaluates the ability to block methylphenidate (MP), a DAT inhibitor drug with similar reinforcing properties to cocaine, induced {open_quotes}high{close_quotes} by prior DAT inhibition. It uses PET and [{sup 11}C]d-threo-methylphenidate to measure the relationship between DAT occupancy prior to administration of MP and the intensity of the subjective perception of the {open_quotes}high{close_quotes} in 8 controls. MP (0.375 mg/kg iv) which was administered as a single injection and also as two sequential doses given 60 minutes apart significantly reduced the ratio of the distribution volume for [{sup 11}C]d-threo-methylphenidate in striatum to that in cerebellum from a baseline of 2.83 {plus_minus} 0.2 to 1.29 {plus_minus} 0.1 at 7 minutes and to 1.37 {plus_minus} 0.2 at 60 minutes after a single injection of MP and to 1.14 {plus_minus} 0.1 at 7 minutes after the second of two sequential MP doses. This corresponds to a DAT occupancy by MP of 84% {plus_minus} 7 at 7more » minutes and of 77% {plus_minus} 6 at 60 minutes after a single injection of MP and of 93% {plus_minus} 7 at 7 after the second of two sequential MP doses. The subjective perception of {open_quotes}high{close_quotes} experienced after the second injection of MP was of a similar magnitude to that experienced after the first injection of MP was of a similar magnitude to that experienced after the first injection, in spite of the very different starting DAT occupancies (0 and 77%, respectively). DAT occupancy was not correlated with the {open_quotes}high{close_quotes}; and one subject with 100% DAT occupancy did not perceive the {open_quotes}high{close_quotes}.« less

Authors:
; ;  [1]
  1. Brookhaven National Lab., Upton, NY (United States)
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States)
OSTI Identifier:
447735
Report Number(s):
CONF-960659-
Journal ID: JNMEAQ; ISSN 0161-5505; CNN: Contract NIDA IR01-DA09490-01; TRN: 97:000961-0015
DOE Contract Number:  
AC02-76CH00016
Resource Type:
Journal Article
Journal Name:
Journal of Nuclear Medicine
Additional Journal Information:
Journal Volume: 37; Journal Issue: Suppl.5; Conference: 43. annual meeting of the Society of Nuclear Medicine, Denver, CO (United States), 3-6 Jun 1996; Other Information: PBD: May 1996
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; COCAINE; DRUG ABUSE; THERAPY; TRACER TECHNIQUES; DOPAMINE; DRUGS; INHIBITION; CARBON 11; LABELLED COMPOUNDS; BIOCHEMISTRY

Citation Formats

Volkow, N D, Wang, G J, Fowler, J S, and SUNY-Stony Brook, NY. Relationship between dopamine transporter occupancy and methylphenidate induced high in humans. United States: N. p., 1996. Web.
Volkow, N D, Wang, G J, Fowler, J S, & SUNY-Stony Brook, NY. Relationship between dopamine transporter occupancy and methylphenidate induced high in humans. United States.
Volkow, N D, Wang, G J, Fowler, J S, and SUNY-Stony Brook, NY. 1996. "Relationship between dopamine transporter occupancy and methylphenidate induced high in humans". United States.
@article{osti_447735,
title = {Relationship between dopamine transporter occupancy and methylphenidate induced high in humans},
author = {Volkow, N D and Wang, G J and Fowler, J S and SUNY-Stony Brook, NY},
abstractNote = {The inhibition of the dopamine transporter (DAT) by cocaine has been shown to be indispensable for its reinforcing properties. The development of drugs that inibit the DAT has become a major target to prevent cocaine`s effects. However prevention of the {open_quotes}high{close_quotes} by DAT inhibitors has never been demonstrated. This study evaluates the ability to block methylphenidate (MP), a DAT inhibitor drug with similar reinforcing properties to cocaine, induced {open_quotes}high{close_quotes} by prior DAT inhibition. It uses PET and [{sup 11}C]d-threo-methylphenidate to measure the relationship between DAT occupancy prior to administration of MP and the intensity of the subjective perception of the {open_quotes}high{close_quotes} in 8 controls. MP (0.375 mg/kg iv) which was administered as a single injection and also as two sequential doses given 60 minutes apart significantly reduced the ratio of the distribution volume for [{sup 11}C]d-threo-methylphenidate in striatum to that in cerebellum from a baseline of 2.83 {plus_minus} 0.2 to 1.29 {plus_minus} 0.1 at 7 minutes and to 1.37 {plus_minus} 0.2 at 60 minutes after a single injection of MP and to 1.14 {plus_minus} 0.1 at 7 minutes after the second of two sequential MP doses. This corresponds to a DAT occupancy by MP of 84% {plus_minus} 7 at 7 minutes and of 77% {plus_minus} 6 at 60 minutes after a single injection of MP and of 93% {plus_minus} 7 at 7 after the second of two sequential MP doses. The subjective perception of {open_quotes}high{close_quotes} experienced after the second injection of MP was of a similar magnitude to that experienced after the first injection of MP was of a similar magnitude to that experienced after the first injection, in spite of the very different starting DAT occupancies (0 and 77%, respectively). DAT occupancy was not correlated with the {open_quotes}high{close_quotes}; and one subject with 100% DAT occupancy did not perceive the {open_quotes}high{close_quotes}.},
doi = {},
url = {https://www.osti.gov/biblio/447735}, journal = {Journal of Nuclear Medicine},
number = Suppl.5,
volume = 37,
place = {United States},
year = {Wed May 01 00:00:00 EDT 1996},
month = {Wed May 01 00:00:00 EDT 1996}
}