Pharmacology of Motor and Somatosensory Skills in Humans

Burkhard      Pleger; Martin      Tegenthoff; Hubert      Dinse; Patrick      Ragert; Peter      Schwenkreis

Abstract

The pharmacological basis of changes in human behaviour and associated cortical reorganization remains poorly understood. Different paradigms have been introduced to alter motor and somatosensory skills in humans. The underlying changes in synaptic efficacy can be modulated by pharmacological agents acting to gate synaptic plasticity. Non-invasive imaging techniques offer the possibility to assess parallel changes in cortical processing. Cellular studies suggest that there might be only few, but very basic mechanisms that control regulation of synaptic transmission. In particular, the γ-aminobutyric acid (GABA) and the N-methyl-D-aspartic acid (NMDA) receptor, a specific subtype of the glutamatergic receptors, are thought to be crucial in synaptic plasticity. Thus, the application of benzodiazepines facilitating the binding of GABA on GABA(A) receptors, and NMDA receptor blockers, were found to prevent learning and associated cortical reorganization. While there are many approaches to block plastic processes, less is known about drugs, which enhance learning and cortical plasticity. Growing evidence from human studies support the suggestion that learning is subject to amplification by amphetamine. Amphetamine however acts non-specific by increasing centrally the levels of dopamine, serotonin, and noradrenaline. Thus, first approaches that intend to scrutinize the apparently ubiquitous role of only one of these neurotransmitter systems used more specifically acting pharmacological agents. In this review we focus on studies that aimed to investigate the pharmacology of the motor and somatosensory system. First, we introduce standards for testing potential effects of a substance. Then, we focus on biochemical mechanisms of learning, before discussing different motor and somatosensory paradigms which were introduced to elicit changes in cortical excitability or organization in animals and humans. Emphasis is placed on the role of inhibitory and excitatory pharmacological agents acting to gate synaptic plasticity in healthy subjects and patients. It is concluded that future studies that investigate the interaction between artificially modulated receptor activity and specific patterns of behaviour in various neurological disorders may help to improve our understanding of how to support recovery of motor and somatosensory function pharmacologically.

Keywords: cortical reorganization, behaviour, dopamine, serotonin, noradrenaline, g-aminobutyric acid, n-methyl-d-aspartic acid

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