Dürtüselli?in N?roanatomik ve N?rokimyasal Temelleri [ Neuroanatomical and Neurochemical Basis of Impulsivity]

摘要

The term ‘impulsivity’ encompasses a multitude of behaviours that are poorly conceived, premature, inappropriate, and that frequently result in unwanted or deleterious outcomes. Impulsivity manifests as impatience carelessness, risk-taking, sensation-seeking and pleasure-seeking, an underestimated sense of harm, and extroversion. Impulsivity is a core symptom of a broad spectrum of psychiatric disorders. Through focusing on different aspects of impulsive behavior, it has proved possible to devise a variety of behavioral paradigms to measure impulsivity in both human and non-human subjects. These can be broadly divided into two categories: those measuring impulsive action or motoric impulsivity, and those measuring impulsive choice or impulsive decision-making. Impulsive action can be broadly defined as the inability to withhold from making a response. Within the framework of behavioral neuroscience and cognitive psychology, impulse control has been described as an active inhibitory mechanism which modulates the internally or externally driven pre-potent desire for primary reinforcers such as food, sex or other highly desirable rewards. This inhibitory control mechanism may provide the substrate by which rapid conditioned responses and reflexes are transiently suppressed, so that slower cognitive mechanisms can guide behavior. This process is referred to as response inhibition. Two of the most common tests used to study inhibitory processes are the goo-go and stop-signal reaction time tasks. Impulsivity is also evident in the making of impulsive decisions or choices as well as in impulsive actions. Here, there is no “pre-potent” response that is primed and then forcibly inhibited, but a decision-making processes. Impulsive decision making or impulsive choice is defined as initiating actions without adequately considering other possible choices or consequences. Impulsive choice is typically measured in the delay discounting paradigm. In tis paradigm, the tendency to prefer small immediate rewards over larger, more delayed reinforcers is measured. ?mpulsive choice is defined by a greater tendency to value or choose smaller, more immediate reinforcers. Impulsivity is a multi-faceted behaviour. This behaviour may be studied by subdividing it into different processes neuroanatomically and neurochemically. Neuroanatomical data support the suggestion that behavioral disinhibition (impulsive action / motoric impulsivity) and delay-discounting (impulsive choice / decision making) differ in the degree to which various components of frontostriatal loops are implicated in their regulation. The dorsal prefrontal cortex does not appear to be involved in mediating impulsive choice, yet does have some role in regulating inhibitory processes. In contrast, there appears to be a pronounced role for the orbitofrontal cortex and basolateral amygdala in controlling impulsive choice. Other structures, however, such as the nucleus accumbens and subthalamic nucleus may be common to both circuits. From the neurochemical perspective, dopamine system and dopamine- 2 (D2) receptors in particular, seems to be closely involved in making impulsive choice. When the noradrenaline system does not function optimally, it might contribute to increased impulsivity. Serotonin might act upon prefrontal cortex to decrease impulsive choices. Interactions between the serotonin and the dopamine systems are important in the regulation of impulsive behaviour. It is possible that various receptor subtypes of the serotonin system may exert differing and even contrasting effects on impulsive behaviour. Although it is very informative to study neurotransmitter systems separately, it should be kept in mind that there are very intimate interactions between the neurotransmitter systems mentioned above. Based on the fact that impulsivity is regulated through multiple neurotransmitters and even more receptors, one may suggest that pharmacotherapy of impulsivity requires a drug acting on more than one receptor. In addition, when considering improving impulsivity for the treatment of a psychiatric disorder, it is always necessary to know which type of impulsive behaviour exists in that particular disorder. Hence, improving impulsivity for the treatment of psychiatric disorders requires tailoring of pharmacological agents in a precise and perhaps in an individualized manner.