Performance enhancement at the cost of potential brain plasticity: neural ramifications of nootropic drugs in the healthy developing brain

Abstract

Cognitive enhancement is perhaps one of the most intriguing and controversial topics in neuroscience today. Currently, the main classes of drugs used as potential cognitive enhancers include psychostimulants (methylphenidate (MPH), amphetamine), but wakefulness-promoting agents (modafinil) and glutamate activators (ampakine) are also frequently used. Pharmacologically, substances that enhance the components of the memory/learning circuits-dopamine, glutamate (neuronal excitation), and/or norepinephrine-stand to improve brain function in healthy individuals beyond their baseline functioning. In particular, non-medical use of prescription stimulants such as MPH and illicit use of psychostimulants for cognitive enhancement have seen a recent rise among teens and young adults in schools and college campuses. However, this enhancement likely comes with a neuronal, as well as ethical, cost. Altering glutamate function via the use of psychostimulants may impair behavioral flexibility, leading to the development and/or potentiation of addictive behaviors. Furthermore, dopamine and norepinephrine do not display linear effects; instead, their modulation of cognitive and neuronal function maps on an inverted-U curve. Healthy individuals run the risk of pushing themselves beyond optimal levels into hyperdopaminergic and hypernoradrenergic states, thus vitiating the very behaviors they are striving to improve. Finally, recent studies have begun to highlight potential damaging effects of stimulant exposure in healthy juveniles. This review explains how the main classes of cognitive enhancing drugs affect the learning and memory circuits, and highlights the potential risks and concerns in healthy individuals, particularly juveniles and adolescents. We emphasize the performance enhancement at the potential cost of brain plasticity that is associated with the neural ramifications of nootropic drugs in the healthy developing brain.

Keywords: ampakine; brain development; cognitive enhancement; methylphenidate; modafinil; synaptic plasticity.

Figure 1

(A) Chemical structure of methylphenidate (Ritalin©). (B) Chemical structure of modafinil (Provigil©). The drug bears a striking resemblance to methylphenidate and other stimulants.

Figure 2

Relationship of dopamine/norepinephrine to prefrontal function. At lower than optimal levels, the PFC is underactive, and the individual suffers from symptoms of ADHD (impulsivity, poor judgment, inattentiveness, motor hyperactivity). As levels rise, the function improves, until cognition and executive function reaches peak performance at optimal levels of dopamine/norepinephrine. As levels of the neurotransmitters continue to rise past the optimal point, cognition again becomes impaired, with the individual showing distractability, impulsivity, stereotypical behaviors and cognitive inflexibility.