The Affective and Neural Correlates of Heroin versus Cocaine Use in Addiction Are Influenced by Environmental Setting But in Opposite Directions

Abstract

Previous studies have shown that individuals with heroin and cocaine addiction prefer to use these drugs in distinct settings: mostly at home in the case of heroin and mostly outside the home in the case of cocaine. Here we investigated whether the context would modulate the affective and neural responses to these drugs in a similar way. First, we used a novel emotional task to assess the affective state produced by heroin or cocaine in different settings, based on the recollections of male and female drug users. Then we used fMRI to monitor neural activity during drug imagery (re-creating the setting of drug use) in male drug users. Consistent with our working hypothesis, the majority of participants reported a shift in the affective valence of heroin from mostly pleasant at home to mostly unpleasant outside the home (p < 0.0001). The opposite shift was observed for cocaine; that is, most participants who found cocaine pleasant outside the home found it unpleasant when taken at home (p < 0.0014). Furthermore, we found a double dissociation, as a function of drug and setting imagery, in BOLD signal changes in the left PFC and caudate, and bilaterally in the cerebellum (all p values <0.01), suggesting that the fronto-striatal-cerebellar network is implicated in the contextualization of drug-induced affect. In summary, we report that the same setting can influence in opposite directions the affective and neural response to psychostimulants versus opiates in humans, adding to growing evidence of distinct substrates for the rewarding effects of these two drug classes.SIGNIFICANCE STATEMENT The rewarding effects of addictive drugs are often thought to depend on shared substrates. Yet, environmental influences can unmask striking differences between psychostimulants and opiates. Here we used emotional tasks and fMRI to explore the influence of setting on the response to heroin versus cocaine in individuals with addiction. Simply moving from one setting to another significantly decreased heroin pleasure but increased cocaine pleasure, and vice versa. Similar double dissociation was observed in the activity of the fronto-striatal-cerebellar network. These findings suggest that the effects of opiates and psychostimulants depend on dissociable psychological and neural substrates and that therapeutic approaches to addiction should take into account the peculiarities of different drug classes and the settings of drug use.

Keywords: addiction; context; emotion; fMRI; opiates; psychostimulants.

Figure 1.

Assessment of affective states. A, Graphic representation of the Circumplex Model of Affect (Russell, 1980). B, Bidimensional representation of affective states used in Experiment 1. This test was developed based on the Circumplex Model of Affect (left) by removing the labels indicating different levels for each dimension and by adding emoticons.

Figure 2.

Outline of the imagery task during fMRI and vividness ratings. A, Outline of the 8 imagery trials during fMRI (2 for each combination of drug and setting). Each trial began with a baseline imagery period of 60 s, during which the participants were asked to imagine relaxing either at home or outside the home. The participants were then asked to imagine using heroin or cocaine in the baseline setting for 120 s (drug imagery). This period was followed by 60 s of rest, during which the participants were asked not to engage in imagery. Finally, the participants were asked to rate the vividness of the imagery on a VAS (1–10 points), by pressing a button. Immediately after completing the VAS, the next trial began. B, Vividness ratings for individual participants.

Figure 3.

Whole-brain analysis map. Map represents regions of significant neuronal activation during the drug imagery period, regardless of drug and setting, relative to the baseline imagery period. Whole-brain analysis conducted in SPM8 using an “omnibus” F contrast revealed significant changes in the regions showed below (P_FWE < 0.05 at the voxel level). Voxels below threshold are not rendered in color.

Figure 4.

Subjective appraisal of the emotional valence of drug experience as a function of drug and setting. Pie charts represent the proportion of participants reporting the affective states detailed in the legend and illustrated in Figure 1B after heroin (A, B) or cocaine (C, D) use. The McNemar's test indicated significant shifts in valence as a function of the setting of drug use. A small proportion of participants reported two affective states (hatched lines) or more (gray).

Figure 5.

BOLD signal changes in the left PFC. Mean (±SEM) BOLD signal changes (A) during the drug imagery task (relative to baseline imagery) in the BA46, BA44, and BA8 obtained by averaging the values of 12 10 s bins calculated using finite impulse response analysis (B). The whole-brain map is the same shown in Figure 3.

Figure 6.

BOLD signal changes in the left caudate and in the cerebellum. Mean (±SEM) BOLD signal changes (A) during the drug imagery task (relative to baseline imagery) in the caudate and cerebellum obtained by averaging the values of 12 10 s bins calculated using finite impulse response analysis (B).