Neurochemical substrates linked to impulsive and compulsive phenotypes in addiction: A preclinical perspective

Abstract

Drug compulsion manifests in some but not all individuals and implicates multifaceted processes including failures in top‐down cognitive control as drivers for the hazardous pursuit of drug use in some individuals. As a closely related construct, impulsivity encompasses rash or risky behaviour without foresight and underlies most forms of drug taking behaviour, including drug use during adverse emotional states (i.e., negative urgency). While impulsive behavioural dimensions emerge from drug‐induced brain plasticity, burgeoning evidence suggests that impulsivity also predates the emergence of compulsive drug use. Although the neural substrates underlying the apparently causal relationship between trait impulsivity and drug compulsion are poorly understood, significant advances have come from the interrogation of defined limbic cortico‐striatal circuits involved in motivated behaviour and response inhibition, together with chemical neuromodulatory influences from the ascending neurotransmitter systems. We review what is presently known about the neurochemical mediation of impulsivity, in its various forms, and ask whether commonalities exist in the neurochemistry of compulsive drug‐motivated behaviours that might explain individual risk for addiction. image

The crosstalk between the “inflamed” mind and the “impulsive” mind: activation of microglia and impulse control disorders

“…Both pro-inflammatory cytokines and serotonin (5-HT) have been implicated in the aetiology of psychiatric disorders. Impulsivity, as most studies reported, is related to lower forebrain 5-HT transmission, altered 5-HT receptor subtypes ratio, and abnormal serotonergic neural signaling to the mPFC and OFC [45]. As mentioned, elevated pro-inflammatory cytokines are associated with impulsivity.…”

“…Elevated pro-inflammatory cytokines could disrupt neurotransmission, related to abnormal impulsivity traits, from any one of the three main aspects: synthesis, reuptake, and release of neurotransmitters [44]. The monoamine systems, including serotonin (5-HT), dopamine (DA), noradrenaline (NA), and non-monoamine neurotransmitters such as glutamate and GABA, are critical biochemical substrates of the impulsivity [45]. 5-HT has been implicated in the inhibition of behaviors, and its depletion has various impacts on different forms of impulsivity.…”

“…There are five subtypes of dopaminergic receptors, blocking some of which would lead to impulsive behaviors. To exemplify, reduced availability of D2-like receptors in the NAcbC and NAcbS would increase delay discounting and premature responding in the 5-CSRTT [45], indicative of promoted impulsivity. However, how neuroinflammation affects these dopaminergic processes is less discussed.…”

Investigating Temporal Memory Strength and Time-Based Impulse Control Using the DRL Task

“…In addition to the behavioral difference between DRL and 5-CSRTT, the neurobiological or psychopharmacological mechanisms of impulsive action evaluated by these two tasks have been considered to be dissociable (D' Amour-Horvat & Leyton, 2014;Jentsch et al, 2014). Despite this, to date, extensive evidence has been largely derived from previous studies using the 5-CSRTT and various kinds of neural or pharmacological manipulations therein (Dalley & Robbins, 2017;Dalley et al, 2008;Jones et al, 2021;Robbins, 2002). In contrast, much less evidence is accumulated from using the DRL task.…”

“…Accumulative evidence suggests that maladaptive impulsivity is a behavioral trait that is prominent in various psychiatric disorders, including ADHD and drug addiction (Jentsch et al, 2014;Jones et al, 2021). In the domain of impulsive action, individual differences measured by 5-CSRTT have been shown to be linked to variations in drug addiction behavior in rats (e.g., Dalley et al, 2007;Diergaarde et al, 2008).…”