Dopamine Regulates Approach-Avoidance in Human Sensation-Seeking

Abstract

Background: Sensation-seeking is a trait that constitutes an important vulnerability factor for a variety of psychopathologies with high social cost. However, little is understood either about the mechanisms underlying motivation for intense sensory experiences or their neuropharmacological modulation in humans.

Methods: Here, we first evaluate a novel paradigm to investigate sensation-seeking in humans. This test probes the extent to which participants choose either to avoid or self-administer an intense tactile stimulus (mild electric stimulation) orthogonal to performance on a simple economic decision-making task. Next we investigate in a different set of participants whether this behavior is sensitive to manipulation of dopamine D2 receptors using a within-subjects, placebo-controlled, double-blind design.

Results: In both samples, individuals with higher self-reported sensation-seeking chose a greater proportion of mild electric stimulation-associated stimuli, even when this involved sacrifice of monetary gain. Computational modelling analysis determined that people who assigned an additional positive economic value to mild electric stimulation-associated stimuli exhibited speeding of responses when choosing these stimuli. In contrast, those who assigned a negative value exhibited slowed responses. These findings are consistent with involvement of low-level, approach-avoidance processes. Furthermore, the D2 antagonist haloperidol selectively decreased the additional economic value assigned to mild electric stimulation-associated stimuli in individuals who showed approach reactions to these stimuli under normal conditions (behavioral high-sensation seekers).

Conclusions: These findings provide the first direct evidence of sensation-seeking behavior being driven by an approach-avoidance-like mechanism, modulated by dopamine, in humans. They provide a framework for investigation of psychopathologies for which extreme sensation-seeking constitutes a vulnerability factor.

Keywords: D2 antagonist; addiction; dopamine; impulsivity; sensation-seeking.

Figure 1.

Sensation-seeking task. In the first part of the task (acquisition phase), participants were presented with a series of forced choice decisions between pairs of abstract fractal images. There were 8 different fractal stimuli (conditioned stimuli [CSs]) with 2 different CSs assigned to each of 4 possible point values (25, 50, 75, or 100 points; with which choice option a particular fractal represented randomised for every participant). Choice pairs were restricted to consist of either adjacent or equal points value stimuli, yielding 10 trial types. The acquisition phase of the task continued for a minimum of 80 trials until participants reached a criterion level of performance, ≥80% higher points value choices over the last 10 trials where a higher points value choice was possible. After this learning stage was completed, participants progressed to the second part of the task (test phase). For the test phase, participants were instructed that all stimuli were associated with the same points value as before but that some of the stimuli were now associated with the chance of receiving a mild electric stimulus (MES) to their nondominant hand (the magnitude of the MES was individually calibrated to be “stimulating but not painful” prior to starting the task). Specifically, one-half of the stimuli became designated as CS+s (chance of MES) and the other half CS-s (no chance of MES) in such a way that trials fell into 1 of 3 types: those where the CS+ was the lower points option, those where the CS+ was the higher points option, and, crucially, those where the CS+ and CS- stimuli were of equal points value. To increase the salience of the tactile stimulus, receipt of the electrical stimulation was probabilistic in both occurrence and timing. The probability of receiving the MES given selection of a CS+ stimulus was 0.75, with the onset of the MES occurring randomly during a 2500-ms inter-stimulus interval (ISI), throughout which participants were presented with a blank screen.

Figure 2.

Interindividual variation in task performance. (A) Individual psychometric functions for probability of choosing the mild electric stimulation (MES; CS+ or MES-associated) option as a function of its relative points (monetary) value, generated for each participant from choice data across all trial types (black circles indicate actual proportionate choice for each trial type). The left/right translation of each function represents the influence of MES value (or θ) on choice, with the gradient of the function determined by the softmax temperature parameter β (a measure of the stochasticity of participants’ choice). A leftward shift in the function reflects a positive effect of opportunity for intense tactile stimulation on choice, that is, greater choice of the MES-associated options than would be expected from points-based choice alone. (B) The value an individual assigned to the opportunity to receive the MES (θ) strongly predicted their difference in choice reaction times (RTs) to CS+ vs CS- stimuli (median RT_CS+ – median RT_CS-; r =-0.690, P<.001). The opportunity for extra sensory stimulation slowed choice of these options in participants for whom it was aversive (low proportionate choice of the CS+; bottom right quadrant), but sped the choice in participants for whom it was appetitive (high choice of the CS+; top left quadrant, orange shading). Black dashed lines indicate 95% confidence intervals. n=45.

Figure 3.

Relationship between task performance and self-report measures. (A) Total self-reported sensation-seeking score was significantly positively related to the value participants assigned to opportunity to receive mild electric stimulation (MES) (r=0.325, P<.05). (B) There was a positive relationship between value assigned to receipt of the intense sensory stimulation (θ) and mean change in visual analogue scale (VAS) “liking” rating of MES-associated (CS+) stimuli following the introduction of the additional electrical stimulation (r=0.368, P<.05). Dashed lines indicate 95% confidence intervals. n =45.

Figure 4.

Effects of haloperidol on the value assigned to intense sensory stimulation. (A) In a second sample of healthy volunteers, the value assigned to intense sensory stimulation (mild electric stimulation [MES]) was significantly related to relative choice reaction time (RT) for MES vs non-MES–associated stimuli on placebo (r=-0.602, P=.001), but not under haloperidol (P>.1; significant decrease in regression coefficient, P<.05). Dashed lines indicate 95% confidence intervals. (B) If subjects were divided into those who approached (showed speeded relative RTs towards, n=8) and those who avoided (showed slowed relative RTs towards, n=20) the opportunity for the intense sensory stimulation under placebo, there was a significant interaction between sensation-seeking group and effect of drug (P<.01). Haloperidol decreased the economic value assigned to the MES only in those participants who exhibited approach reactions towards MES-associated stimuli under normal conditions (high-sensation seekers [HSS]; cf low-sensation seekers [LSS]). Error bars represent SEM. **P=.01, ns P>.10, drug vs placebo. n=28.