title: Expectation enhances the regional brain metabolic and the reinforcing effects of stimulants in cocaine abusers.
abstract: The reinforcing effects of drugs of abuse result from the complex interaction between pharmacological effects and conditioned responses. Here we evaluate how expectation affects the response to the stimulant drug methylphenidate in 25 cocaine abusers. The effects of methylphenidate (0.5 mg/kg, i.v.) on brain glucose metabolism (measured by [18F]deoxyglucose-positron emission tomography) and on its reinforcing effects (self-reports of drug effects) were evaluated in four 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. Methylphenidate increased brain glucose metabolism, and the largest changes were in cerebellum, occipital cortex, and thalamus. The increases in metabolism were approximately 50% larger when methylphenidate was expected than when it was not, and these differences were significant in cerebellum (vermis) and thalamus. In contrast, unexpected methylphenidate induced greater increases in left lateral orbitofrontal cortex than when it was expected. Methylphenidate-induced increases in self-reports of "high" were also approximately 50% greater when subjects expected to receive it than when they did not and were significantly correlated with the metabolic increases in thalamus but not in cerebellum. These findings provide evidence that expectation amplifies the effects of methylphenidate in brain and its reinforcing effects. They also suggest that the thalamus, a region involved with conditioned responses, may mediate the enhancement of the reinforcing effects of methylphenidate by expectation and that the orbitofrontal cortex mediates the response to unexpected reinforcement. The enhanced cerebellar activation with expectation may reflect conditioned responses that are not linked to conscious responses.
authors.affiliation: Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA. nvolkow@nida.nih.gov
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
authors.forename: Gene-Jack
authors.initials: GJ
authors.lastname: Wang
authors.forename: Yemin
authors.initials: Y
authors.lastname: Ma
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Fowler
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Laurence
authors.initials: L
authors.lastname: Maynard
authors.forename: Frank
authors.initials: F
authors.lastname: Telang
authors.forename: Paul
authors.initials: P
authors.lastname: Vaska
authors.forename: Yu-Shin
authors.initials: YS
authors.lastname: Ding
authors.forename: Christopher
authors.initials: C
authors.lastname: Wong
authors.forename: James M
authors.initials: JM
authors.lastname: Swanson
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000523:psychology*; D003213:Conditioning, Psychological; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D012054:Reinforcement, Psychology; D014055:Tomography, Emission-Computed
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D005947:Glucose