Inter-individual differences in the impulsive/compulsive dimension: deciphering related dopaminergic and serotonergic metabolisms at rest

Abstract

Several impulse control disorders such as ADHD, mania, personality disorders or substance abuse share common behavioural traits, like impulsiveness, risk-taking or inflexible behaviour. These disorders are treated with drugs targeting dopamine (DA) and/or serotonin (5-HT). However, the patient's monoamine imbalance that these neurotransmitters compensate is unclear. This study aims to investigate the patterns of DA and 5-HT metabolisms at rest within selected brain regions related to inter-individual variability in six main components of impulsivity/compulsivity (anticipatory hyperactivity, premature responses, delay discounting, risk-taking, perseveration, flexibility). Rats with adaptive and highly inadaptive behaviours were identified in each task and a sensitive biochemical approach allowed mapping of post-mortem endogenous monoamine tissue content in 20 brain areas. Distinct patterns of 5-HT and DA metabolisms were revealed according to the behavioural traits. Except for hyperactive responses, lower control of actions was mainly associated with a lower DA or 5-HT metabolism in prefrontal and/or subcortical areas (i.e. in orbitofrontal cortex (DA), amygdala and anterior cingulate cortex (5-HT) for inflexible and risk-prone rats). Our results reveal the complex nature of behavioural traits related to impulse control disorders through their associated monoaminergic networks at rest, paving the way for understanding the link between mental disorders and drug therapeutic actions.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.

Keywords: dopamine; impulsivity; inflexibility; monoamine tissue content; risk-taking; serotonin.

Figure 1.

Inter-individual differences in impulsive/compulsive actions and monoamines turnovers at rest. The figure reports the inter-individual differences in fixed consecutive number of 16 lever press schedule (FCN16) (a), in the anticipatory activity (d) or in perseverative behaviour (g), the mean behavioural performances in subgroups for each task (b,e,h) and the corresponding regional changes of serotonergic and dopaminergic turnovers (mean ± s.e.m.) measured across 20 brain regions (c,f,i). Premature responses in FCN (a) are reflected by the percentage of rewarded chains distinguishing rats with impulsive (IMP-FCN, scores <75% presses) and non-impulsive behaviour (NIMP-FCN, scores >85%); (b) frequency distribution (%) of chain length and mean percentage of rewarded chains (insert) of the two groups. In the anticipatory activity during FI (d), rats displayed impulsive (IMP-FI, scores >180 presses) and non-impulsive behaviour (NIMP-FI, scores <80 presses); (e) mean number of lever presses by each group during the 1 min FI component as a function of 10 s segments of the FI period. Perseverative behaviour (g) of rats during EXT highlighted compulsive (COMP-EXT, scores >110 presses) and non-compulsive behaviours (NCOMP-EXT, scores <55 presses); (i) mean number of lever presses by each group during the 5 min EXT component as a function of 30 s segments of the EXT period. In (b,e,h) dotted line or crosses indicate median score. °p < 0.001; **p < 0.01; *p < 0.05 (Student's t test).

Figure 2.

Inter-individual differences in impulsive/compulsive actions and monoamines turnovers at rest. The figure reports the inter-individual differences in the DDT (a), the rat gambling task (RGT-reversal, d) and the emergence task (g), the mean behavioural performances in subgroups for each task (b,e,h) and the corresponding regional changes of serotonergic and dopaminergic turnovers (mean ± s.e.m.) measured across 20 brain regions (c,f,i). In the DDT (a), impulsive choice was reflected by the mean percentage of choice for the large reinforcement when a delay (from 10 to 40 s) occurs, highlighting impulsive (IMP-DD, scores <35%) and non-impulsive behaviour (NIMP-DD, scores >53%); (b) Percentage choice of the two groups for the large reinforcement according to the length of the delay before obtaining it. Comparisons with chance level (50%, dotted line): significant differences with chance for scores above or below 50% show a preference for the large or the small reward respectively. Flexibility index in the RGT-reversal (d) showed inflexible (INFLEX) and flexible behaviour (FLEX); (e) time-course of reversed choice percentage in the RGT-reversal task for FLEX and INFLEX. Dotted line indicates 50% level (no preference). The index of risk-taking in the emergence task (g) showed risk-prone (RISK, scores <170) and risk avoiders (NORISK, scores >810); (h) Mean values of the risk-taking index for RISK and 0RISK (s). °p < 0.001; **p < 0.01; *p < 0.05 (Student's t test).