Alterations in the impulse-control balance, and in its neural bases, have been reported in obesity and eating disorders (EDs). Neuroimaging studies suggest a role of fronto-parietal networks in impulsive behaviour, with evaluation and anticipatory processes additionally recruiting meso-limbic regions. However, whether distinct facets of cognitive and motor impulsivity involve common vs. specific neural correlates remains unclear. We addressed this issue through Activation Likelihood Estimation (ALE) meta-analyses of fMRI studies on delay discounting (DD) and go/no-go (GNG) tasks, alongside conjunction and subtraction analyses. We also performed systematic reviews of neuroimaging studies using the same tasks in individuals with obesity or EDs. ALE results showed consistent activations in the striatum, anterior/posterior cingulate cortex, medial/left superior frontal gyrus and left supramarginal gyrus for impulsive choices in DD, while GNG tasks elicited mainly right-lateralized fronto-parietal activations. Conjunction and subtraction analyses showed: i) common bilateral responses in the caudate nucleus; ii) DD-specific responses in the ventral striatum, anterior/posterior cingulate cortex, left supramarginal and medial frontal gyri; iii) GNG-specific activations in the right inferior parietal cortex. Altered fronto-lateral responses to both tasks are suggestive of dysfunctional cortico-striatal balance in obesity and EDs, but these findings are controversial due to the limited number of studies directly comparing patients and controls. Overall, we found evidence for distinctive neural correlates of the motor and cognitive facets of impulsivity: the right inferior parietal lobe underpins action inhibition, whereas fronto-striatal regions and the left supramarginal gyrus are related to impulsive decision-making. While showing that further research on clinical samples is required to better characterize the neural bases of their behavioural changes, these findings help refining neurocognitive model of impulsivity and highlight potential translational implications for EDs and obesity treatment.

BACKGROUND: The 5-HT2A receptor is the major target of classic hallucinogens. Both DOI (2,5-dimethoxy-4-iodoamphetamine) and lisuride act at 5-HT2A receptors, and lisuride shares comparable affinity with DOI and acts as a partial agonist at 5-HT2A receptors. However, not like DOI, lisuride lacks hallucinogenic properties. Impulsive decision-making refers to the preference for an immediate small reinforcer (SR) over a delayed large reinforcer (LR).
OBJECTIVE: The current study aims to compare the effects of DOI and lisuride on impulsive decision-making and further to investigate the possible receptor mechanisms responsible for the actions of the two drugs.
METHODS: Impulsive decision-making was evaluated in male Sprague-Dawley rats by the percentage of choice for the LR in delay discounting task (DDT). Delay to the LR changed in an ascending order (0, 4, 8, 16, and 32 s) across one session.
RESULTS: DOI (0.5 and 1.0 mg/kg) increased impulsive decision-making, and the effects of DOI (1.0 mg/kg) were blocked by the 5-HT2A receptor antagonist ketanserin (1.0 mg/kg) rather than the 5-HT2C receptor antagonist SB-242084 (1.0 mg/kg). Contrarily, lisuride (0.1, 0.3, and 0.5 mg/kg) decreased impulsive decision-making. The effects of lisuride (0.3 mg/kg) were not antagonized by ketanserin (1.0 mg/kg), selective 5-HT1A antagonist WAY-100635 (1.0 mg/kg), or selective dopamine D4 receptor antagonist L-745870 (1.0 mg/kg) but were attenuated by the selective dopamine D2/D3 receptor antagonist tiapride (40 mg/kg).
CONCLUSIONS: DOI and lisuride have contrasting effects on impulsive decision-making via distinct receptors. DOI-induced increase of impulsivity is mediated by the 5-HT2A receptor, while lisuride-induced inhibition of impulsivity is regulated by the dopamine D2/D3 receptor.