Impulsivity, broadly defined as action without foresight, is a component of numerous psychiatric illnesses including attention deficit/hyperactivity disorder (ADHD), mania and substance abuse. In order to investigate the mechanisms underpinning impulsive behavior, the nature of impulsivity itself needs to be defined in operational terms that can be used as the basis for empirical investigation. Due to the range of behaviors that the term impulsivity describes, it has been suggested that impulsivity is not a unitary construct, but encompasses a variety of related phenomena that may differ in their biological basis. Through fractionating impulsivity into these component parts, it has proved possible to devise different behavioral paradigms to measure various aspects of impulsivity in both humans and laboratory animals. This review describes and evaluates some of the current behavioral models of impulsivity developed for use with rodents based on human neuropsychological tests, focusing on the five-choice serial reaction time task, the stop-signal reaction time task and delay-discounting paradigms. Furthermore, the contributions made by preclinical studies using such methodology to improve our understanding of the neural and neurochemical basis of impulsivity and ADHD are discussed, with particular reference to the involvement of both the serotonergic and dopaminergic systems, and frontostriatal circuitry.
The orbitofrontal cortex (OFC) and basolateral nucleus of the amygdala (BLA) share many reciprocal connections, and a functional interaction between these regions is important in controlling goal-directed behavior. However, their relative roles have proved hard to dissociate. Although injury to these brain regions can cause similar effects, it has been suggested that the resulting impairments arise through damage to different, yet converging, cognitive processes. Patients with OFC or amygdala lesions exhibit maladaptive decision making and aberrant social behavior often described as impulsive. Impulsive choice may be measured in both humans and rodents by evaluating intolerance to delay of reinforcement. Rats with excitotoxic lesions of the BLA and OFC were tested on such a delay-discounting procedure. Although lesions of the BLA increased choice of the small immediate reward, indicating greater impulsivity, OFC lesions had the opposite effect, increasing preference for the larger but delayed reward. The fact that the delay did not devalue the large reward to such an extent in OFC-lesioned animals supports the suggestion that the OFC is involved in updating the incentive value of outcomes in response to devaluation. In contrast, the BLA-lesioned animals markedly decreased their preference for the large reward when it was delayed, potentially because of an inability to maintain a representation of the reward in its absence. This is the first time that lesions to these two structures have produced opposite behavioral effects, indicating their distinct contributions to cognition.
Pathological gambling (PG) is characterized by persistent, maladaptive gambling behavior, which disrupts personal and professional life. Animal models of gambling behavior could make a significant contribution to improving our understanding of the neural and neurochemical basis of gambling, and the treatment of PG. When gambling, failing to win critically results in the loss of resources wagered as well as the absence of additional gain. Here, we have incorporated these concepts into a novel rat gambling task (rGT), based, in part, on the 'Iowa' gambling task (IGT) commonly used clinically to measure gambling-like behavior. Rats choose among four different options to earn as many sugar pellets as possible within 30 min. Each option is associated with the delivery of a different amount of reward, but also with a different probability and duration of punishing time-out periods during which reward cannot be earned. The schedules are designed such that persistent choice of options linked with larger rewards result in fewer pellets earned per unit time. Rats learn to avoid these risky options to maximize their earnings, comparable with the optimal strategy in the IGT. Both d-amphetamine and the 5-HT 1A receptor agonist, 8-OH-DPAT, impaired task performance. In contrast, the dopamine D 2 receptor antagonist, eticlopride, improved performance, whereas the D 1 receptor antagonist, SCH23390, had no effect. These data suggest that both serotonergic and dopaminergic agents can impair and improve gambling performance, and indicate that the rGT will be a useful tool to study the biological basis of gambling.
These data support the view that serotonergic regulation of impulsive behaviour through different members of the 5-HT(2) receptor family is functionally heterogeneous. Although both 5-HT(2A) and 5-HT(2C) receptors participate in controlling this form of impulsive action, their relative contribution may depend on the endogenous state of the 5-HT system.
Reducing levels of 5-HT in the central nervous system has been associated with increases in impulsive behavior. However, the impulsivity construct describes a wide range of behaviors, including the inability to withhold a response, intolerance to delay of reward and perseveration of a nonrewarded response. Although these behaviors are generally studied using instrumental paradigms, impulsivity may also be reflected in simple Pavlovian tasks such as autoshaping and conditioned activity. This experiment aimed to characterize further the effects of central 5-HT depletion and to investigate whether different behavioral measures of impulsivity are inter-related, thus validating the construct. Rats received intracerebroventricular (ICV) infusions of vehicle (n ¼ 10) or the serotonergic neurotoxin 5,7-dihydroxytryptamine (n ¼ 12) which depleted forebrain 5-HT levels by about 90%. Lesioned animals showed significant increases in the speed and number of responses made in autoshaping, increased premature responding on a simple visual attentional task, enhanced expression of locomotor activity conditioned to food presentation, yet no change in impulsive choice was observed, as measured by a delay-discounting paradigm. Significant positive correlations were found between responses made in autoshaping and the level of conditioned activity, indicating a possible common basis for these behaviors, yet no correlations were found between other behavioral measures. These data strengthen and extend the hypothesis that 5-HT depletion increases certain types of impulsive responding. However, not all measures of impulsivity appear to be uniformly affected by 5-HT depletion, or correlate with each other, supporting the suggestion that impulsivity is not a unitary construct.
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