A Role for Serotonin in Modulating Opposing Drive and Brake Circuits of Impulsivity

Abstract

Impulsivity generally refers to a deficit in inhibition, with a focus on understanding the neural circuits which constitute the “brake” on actions and gratification. It is likely that increased impulsivity can arise not only from reduced inhibition, but also from a heightened or exaggerated excitatory “drive.” For example, an action which has more vigor, or is fueled by either increased incentive salience or a stronger action-outcome association, may be harder to inhibit. From this perspective, this review focuses on impulse control as a competition over behavioral output between an initially learned response-reward outcome association, and a subsequently acquired opposing inhibitory association. Our goal is to present a synthesis of research from humans and animal models that supports this dual-systems approach to understanding the behavioral and neural substrates that contribute to impulsivity, with a focus on the neuromodulatory role of serotonin. We review evidence for the role of serotonin signaling in mediating the balance of the “drive” and “brake” circuits. Additionally, we consider parallels of these competing instrumental systems in impulsivity within classical conditioning processes (e.g., extinction) in order to point us to potential behavioral and neural mechanisms that may modulate the competing instrumental associations. Finally, we consider how the balance of these competing associations might contribute to, or be extracted from, our experimental assessments of impulsivity. A careful understanding of the underlying behavioral and circuit level contributions to impulsivity is important for understanding the pathogenesis of increased impulsivity present in a number of psychiatric disorders. Pathological levels of impulsivity in such disorders are likely subserved by deficits in the balance of motivational and inhibitory processes.

Pharmacological Mechanism of Ketamine in Suicidal Behavior Based on Animal Models of Aggressiveness and Impulsivity: A Narrative Review

“…Identification of the mechanisms of pathophysiology, suicide risk factors of neuropsychological vulnerabilities, cognitive deficits, the endophenotypes of sub-groups of patients presenting with suicide ideations/suicidality, as well as the role of critical interactions between genetic and epigenetic factors associated with suicidal behavior may help to solve this issue. Studies of deficits in the balance of motivational and inhibitory processes may be key factors to solve these issues [180]. In addition, neural and behavioral motivational processes highlight the importance of reward circuitry in ketamine's mechanism of action in motivational symptoms [181].…”

An integrative sensor of body states: how the mushroom body modulates behavior depending on physiological context

“…These results challenge the assumption that most of the DAN activity is related to decision-making, top-down motor control, or prediction error detection from sensory feedback and instead provide evidence that walk itself and somatosensory bottom-up stimuli are largely responsible for the observed activity patterns ( Aimon et al 2023 ). Interestingly, while DAN activity increases with locomotion, specific serotonin signals are strongly inhibited when the fly engages in walking ( Aimon et al 2023 ), reminiscent of a functional discrimination between go and no-go signals by dopamine and serotonin in mammals ( Desrochers et al 2022 ).…”

Prenatal maternal stress and offspring aggressive behavior: Intergenerational and transgenerational inheritance

“…Brain imaging studies conducted in humans by Barrash et al (2022) and Grafman et al (1996) and a systematic review of neural, cognitive, and clinical studies of anger and aggression by Richard et al (2022) have also provided more evidence that disruption of the frontocorticoamygdalar circuit as well as ventromedial frontal lobe lesions are linked to aggressive behaviors. The monoaminergic system particularly the 5-HT system has been greatly implicated in the formation of this circuit and other circuits subserving emotional behavior (Rainnie, 1999;Desrochers et al, 2022). At the molecular level prenatal maternal stress has been shown to influence amygdala expression of 5-HT1A receptors as well as GABAergic function (Ehrlich et al, 2015).…”