Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli

Abstract

Drug abuse and dependence define behavioral states involving increased allocation of behavior towards drug seeking and taking at the expense of more appropriate behavioral patterns. As such, addiction can be viewed as increased control of behavior by the desired drug (due to its unconditioned, rewarding properties). It is also clear that drug-associated (conditioned) stimuli acquire heightened abilities to control behaviors. These phenomena have been linked with dopamine function within the ventral striatum and amygdala and have been described specifically in terms of motivational and incentive learning processes. New data are emerging that suggest that regions of the frontal cortex involved in inhibitory response control are directly affected by long-term exposure to drugs of abuse. The result of chronic drug use may be frontal cortical cognitive dysfunction, resulting in an inability to inhibit inappropriate unconditioned or conditioned responses elicited by drugs, by related stimuli or by internal drive states. Drug-seeking behavior may thus be due to two related phenomena: (1) augmented incentive motivational qualities of the drug and associated stimuli (due to limbic/amygdalar dysfunction) and (2) impaired inhibitory control (due to frontal cortical dysfunction). In this review, we consider the neuro-anatomical and neurochemical substrates subserving inhibitory control and motivational processes in the rodent and primate brain and their putative impact on drug seeking. The evidence for cognitive impulsivity in drug abuse associated with dysfunction of the frontostriatal system will be discussed, and an integrative hypothesis for compulsive reward-seeking in drug abuse will be presented.

Extended Access to Cocaine Self-Administration Produces Long-Lasting Prefrontal Cortex-Dependent Working Memory Impairments

“…Similar neural changes may be responsible for the cognitive impairments observed in humans with drug addiction (Goldstein and Volkow, 2002;Pfefferbaum et al, 1998;Bechara, 2005;Franklin et al, 2002;Jentsch and Taylor, 1999;Rogers and Robbins, 2001).…”

Acute Δ9-Tetrahydrocannabinol-Induced Deficits in Reversal Learning: Neural Correlates of Affective Inflexibility

“…Inflexibility in stimulusreward associations may contribute to continued propensity to self-administer drugs, as the reward value of the drug or associated stimuli may not be updated in response to devaluation by the emergence of tolerance or adverse social consequences (Bolla et al, 2002;Jentsch and Taylor, 1999;Volkow and Fowler, 2000). Deficits in reversal learning may reflect either a failure in learning new associations between stimuli or deficits in the ability to inhibit previously learned stimulus-reward contingencies.…”

“…Possible deleterious effects of marijuana use on cognitive flexibility, a cardinal feature of the primate prefrontal cortex (PFC) (Dias et al, 1996a;Owen et al, 1991), may be of particular importance; inflexibility in attentional and affective control may be deleterious to intellectual and social functioning (Pope and YurgelunTodd, 1996), and may underlie perseveration to continued drug administration (Bolla et al, 2002;Jentsch and Taylor, 1999;Volkow and Fowler, 2000). While some studies have indicated that impairments in mental flexibility persist after approximately 1 day (Pope and Yurgelun-Todd, 1996) and 28 days of abstinence from marijuana (Bolla et al, 2002), other studies performed at similar time points have yielded negative or minimal results (Fletcher et al, 1996;Pope et al, 2001).…”

Evidence for GABA‐A receptor dysregulation in gambling disorder: correlation with impulsivity

“…Based upon our previous findings in alcohol and opiate dependence for the [ 11 C]Ro15‐4513 PET analysis, we selected right hippocampus and NAc as a priori ROIs, and we chose two additional a priori ROIs based upon their established role in impulse control: OFC and amygdala (Goldstein and Volkow 2002; Jentsch and Taylor 1999; Ko et al 2015; Nikolova et al 2016). As previous work (Clark et al 2012; Michalczuk et al 2011) has shown that NU, as a mood‐related subgroup of impulsivity, is most strongly associated with GD, we chose to test for correlations between UPPS‐P NU and a priori selected brain regions.…”