Effects of expectation on the brain metabolic responses to methylphenidate and to its placebo in non-drug abusing subjects.

Full Abstract

The response to drugs is affected by expectation, which in turn is sensitive to prior drug experiences. Here, we evaluate the effects of expectation on the responses to intravenous methylphenidate (0.5 mg/kg) in fifteen subjects who had minimal experience with stimulant drugs. We used positron emission tomography to measure brain glucose metabolism, which we used as a marker of brain function and tested them under four randomized conditions (1) expecting placebo and receiving placebo; (2) expecting placebo and receiving methylphenidate; (3) expecting methylphenidate and receiving methylphenidate; (4) expecting methylphenidate and receiving placebo. We show that methylphenidate-induced decreases in striatum were greater when subjects expected to receive methylphenidate than when they were not expecting it. We also show that the subjects' expectations affected their responses to placebo. That is, when subjects expected to receive methylphenidate but received placebo there were significant increases in ventral cingulate gyrus (BA 25) and nucleus accumbens (regions involved with emotional reactivity and reward). The effect was largest in subjects who, because of experimental randomization, had not experienced methylphenidate. Because subjects were told that methylphenidate could be experienced as pleasant, unpleasant or devoid of subjective effects these results suggest the involvement of the ventral cingulate and of the nucleus accumbens in processing expectation for "uncertain drug effects". Thus, the state of expectation needs to be considered as a variable modulating the reinforcing and therapeutic effects of drugs even in subjects who have no prior experience with the drug.

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Author information

Author/s: Volkow, Nora D (ND); Wang, Gene-Jack (GJ); Ma, Yeming (Y); Fowler, Joanna S (JS); Wong, Christopher (C); Jayne, Millard (M); Telang, Frank (F); Swanson, James M (JM);

Affiliation: National Institute on Drug Abuse, Bethesda, MD 20892, USA. nvolkow(-atsign-)nida.nih.gov

Journal and publication information

Publication Type: Clinical Trial; Journal Article; Research Support, N.I.H., Intramural; Research Support, U.S. Gov't, Non-P.H.S.

Journal: NeuroImage (Neuroimage), published in United States. (Language: eng)

Reference: 2006-Oct; vol 32 (issue 4) : pp 1782-92

Dates: Created 2006/09/11; Completed 2006/11/30;

PMID: 16757181, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adult
Blood Pressure - drug effects; physiology
Brain - radionuclide imaging
Brain Chemistry - drug effects
Central Nervous System Stimulants - pharmacology
Dopamine - physiology
Dopamine Plasma Membrane Transport Proteins - metabolism
Fluorodeoxyglucose F18 - diagnostic use
Gyrus Cinguli - drug effects; metabolism; radionuclide imaging
Heart Rate - drug effects; physiology
Humans

Humans
Male
Methylphenidate - pharmacology
Neostriatum - drug effects; metabolism; radionuclide imaging
Placebo Effect
Positron-Emission Tomography
Prefrontal Cortex - drug effects; metabolism; radionuclide imaging
Radiopharmaceuticals - diagnostic use
Reward
Set (Psychology)
Substance-Related Disorders - psychology

Associated Chemicals: Central Nervous System Stimulants (0) ; Dopamine Plasma Membrane Transport Proteins (0) ; Radiopharmaceuticals (0) ; Methylphenidate (113-45-1) ; Dopamine (51-61-6) ; Fluorodeoxyglucose F18 (63503-12-8)

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