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Impact of Psychoactive Drugs

One major aspect of learning is the ability to encode and recall new material or a new function. A neurobiological correlate of learning and memory is ► long-term potentiation (LTP). In LTP, ► synaptic plasticity is evoked by repeated and synchronized firing of pre- and post-synaptic neurons. Thus, all substances that induce or enhance LTP might support or augment learning capacities. Several lines of evidence suggest that ► glutamate metabolism and in particular N-methyl-D-aspartate (NMDA) agonists facilitate LTP induction.

Animal experiments have also indicated other neurotransmitters that are presumably involved in learning. For example, in rats the acquisition of motor skills is improved by noradrenergic substances. Lesions of dopami-nergic neurons can produce cognitive deficits and impair attentional processes which are relevant for learning abilities.

In some learning paradigms, e.g., the serial reaction time task, it is possible to follow the process of learning and to detect the development of implicit and explicit knowledge. In most paradigms, however, it is rather tested whether learning had occurred and whether the application of a psychoactive drug had been able to speed up the learning process or the amount of what had been learnt.

Non-Verbal Learning in Humans

Dopaminergic Drugs levodopa in the motor system is not necessarily generalized to other systems.

Patient Groups In stroke patients, several studies using multiple or single doses of levodopa have been published.

Healthy Subjects The application of a single dose of ► levodopa (100 mg) was able to improve a training-induced motor memory. The task consisted of practising of thumb movements in a different direction than thumb movements evoked by transcranial magnetic stimulation (TMS). After the training period, TMS induced thumb movements in the new, practised direction. In young subjects, the encoding process of this movement was accelerated by levodopa. Elderly subjects performed worse in this task but improved their motor memory encoding by intake of levodopa to levels present in younger subjects (Floel et al. 2005a; Figs. 1 and 2). Presumably, older subjects have a subclinical dopaminergic deficit per se. Application of 300 mg levodopa induced a small, but significant improvement of motor functions even without training. This effect was only seen in elderly, but not in young subjects. In a study that used a tactile coactivation protocol to induce non-associative learning in the so-matosensory system, tactile two-point discrimination was only improved after placebo, but not after levodopa application, suggesting that a potential beneficial effect of

Verbal and Non-Verbal Learning in Humans. Fig. 1. (a)

Experimental design. L-Dopa/placebo was administered at time 0 in each session, followed by determination of transcranial magnetic stimulation (TMS)-evoked thumb movement directions at baseline (60 min after drug intake) and after 10, 20, and 30 (post) min of training (downward arrows). Training consisted of three blocks of brisk thumb movements performed at 1 Hz in the direction opposite to the baseline TMS-evoked thumb movement direction (T). Fatigue, attention towards the training task, blood pressure, and heart rate were assessed four times during the experiment (upward arrows). (b) Diagram showing measurement of thumb movements with an accelerometer positioned on the distal interphalangeal joint (rectangle on the thumb). Baseline TMS-evoked thumb movements in this example fell in a flexion-adduction direction (thin solid arrow). Training voluntary thumb motions were performed in the opposite direction (extension-abduction, thick solid arrow). At the end of the training period, we measured the percentage of TMS-evoked thumb movements falling in the training target zone (TTZ), the end point measure of the study. (From Floel et al. 2005a.)

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