D-amphetamine boosts language learning independent of its cardiovascular and motor arousing effects

TY - JOUR

T1 - D-amphetamine boosts language learning independent of its cardiovascular and motor arousing effects

AU - Breitenstein, Caterina

AU - Wailke, Stefanie

AU - Bushuven, Stefan

AU - Kamping, Sandra

AU - Zwitserlood, Pienie

AU - Ringelstein, E Bernd

AU - Knecht, Stefan

PY - 2004/9

Y1 - 2004/9

N2 - D-Amphetamine (AMPH) was effective in a number of studies on motor and language recovery after stroke, but given safety concerns, its general use after stroke is still debated. Most stroke patients are excluded from treatment because of a significant risk of cardiovascular dysregulation. AMPH acts on multiple transmitter systems, and mainly the noradrenergic actions are related to the cardiovascular effects. If AMPH's cardiovascular and arousal effects were correlated with its plasticity-enhancing effects in humans, this would imply that desired and undesired effects are inevitably tied. If not, improved cerebral reorganization may not be mediated by AMPH's arousing effects and could be achieved with substances lacking the undesired cardiovascular effects. As a model for language recovery after stroke, we used a prospective, randomized, double-blind, placebo-controlled design and taught 40 healthy male subjects an artificial vocabulary of 50 concrete nouns over the course of five consecutive training days (high-frequency training). The associative learning principle involved higher co-occurrences of 'correct' picture-pseudoword pairings as compared to 'incorrect' pairings. Subjects received either AMPH (0.25 mg/kg) or placebo 90 min prior to training on each day. Novel word learning was significantly faster and better in the AMPH as compared to the placebo group. Increased learning success was maintained 1 month post-training. No correlation was found between training success and drug-induced increases in blood pressure, heart rate, or a facilitation of simple motor reaction time. Our data show that AMPH's plasticity-enhancing effect in humans is not related to its cardiovascular arousal. This suggests that the beneficial effects in stroke patients could also be obtained by less cardiovascular active drugs.

AB - D-Amphetamine (AMPH) was effective in a number of studies on motor and language recovery after stroke, but given safety concerns, its general use after stroke is still debated. Most stroke patients are excluded from treatment because of a significant risk of cardiovascular dysregulation. AMPH acts on multiple transmitter systems, and mainly the noradrenergic actions are related to the cardiovascular effects. If AMPH's cardiovascular and arousal effects were correlated with its plasticity-enhancing effects in humans, this would imply that desired and undesired effects are inevitably tied. If not, improved cerebral reorganization may not be mediated by AMPH's arousing effects and could be achieved with substances lacking the undesired cardiovascular effects. As a model for language recovery after stroke, we used a prospective, randomized, double-blind, placebo-controlled design and taught 40 healthy male subjects an artificial vocabulary of 50 concrete nouns over the course of five consecutive training days (high-frequency training). The associative learning principle involved higher co-occurrences of 'correct' picture-pseudoword pairings as compared to 'incorrect' pairings. Subjects received either AMPH (0.25 mg/kg) or placebo 90 min prior to training on each day. Novel word learning was significantly faster and better in the AMPH as compared to the placebo group. Increased learning success was maintained 1 month post-training. No correlation was found between training success and drug-induced increases in blood pressure, heart rate, or a facilitation of simple motor reaction time. Our data show that AMPH's plasticity-enhancing effect in humans is not related to its cardiovascular arousal. This suggests that the beneficial effects in stroke patients could also be obtained by less cardiovascular active drugs.

KW - Adult

KW - Affect

KW - Arousal

KW - Central Nervous System Stimulants

KW - Dextroamphetamine

KW - Double-Blind Method

KW - Hemodynamics

KW - Humans

KW - Language

KW - Learning

KW - Male

KW - Motivation

KW - Motor Activity

KW - Neuronal Plasticity

KW - Neuropsychological Tests

KW - Reaction Time

KW - Stimulation, Chemical

U2 - 10.1038/sj.npp.1300464

DO - 10.1038/sj.npp.1300464

M3 - SCORING: Journal article

C2 - 15114342

VL - 29

SP - 1704

EP - 1714

JO - NEUROPSYCHOPHARMACOL

JF - NEUROPSYCHOPHARMACOL

SN - 0893-133X

IS - 9

ER -