Paradoxical effects of drugs on cognitive function: the neuropsychopharmacology of the dopamine and other neurotransmitter systems

Neurotransmitters are the means by which one neuron influences the action of another. Abnormalities in neurotransmitter function are implicated in a variety of neurological and neuropsychiatric disorders and drugs that influence the neurotransmitter systems are often used in treating the symptoms of such disorders. The effects of these drugs can be paradoxical. A small dose of a pharmacological agent might have entirely the opposite effect to a large dose, a drug may improve one ability whilst impairing another, a drug may have opposite effects in different populations or opposite effects in the same individual at different times. In this chapter, we illustrate these effects using clinical data and data from healthy volunteers in experimental studies. With one of the best studied neuromodulators – dopamine – as our focus, we introduce key principles that can help to explain these apparent paradoxes. First, the effect of a drug depends on baseline levels of the neurotransmitter already in the system. When baseline levels are low, a given pharmacological dose can increase function closer to an optimal level. When baseline levels are high, the same dose can over-stimulate the system and trigger compensatory mechanisms that reduce performance on a given task. Second, a drug could have quite different effects in different brain regions. Accordingly, a function that is predominantly influenced by one region may be enhanced, whilst another function, more dependent on another region, may be impaired. In the final section of the chapter, we turn to attention deficit hyperactivity disorder (ADHD).