The intersection of empathy and addiction

Abstract

Empathy, the ability to perceive the affective state of another, is a complex process that is integral to many of the prosocial behaviors expressed in humans and across the animal kingdom. Research into the behavioral and neurobiological underpinnings of empathic behaviors has increased in recent years. Growing evidence suggests changes in empathy may contribute to a myriad of psychiatric illnesses, including substance use disorder (SUD). Indeed, both clinical and preclinical research in SUD demonstrates a strong relationship between drug taking or relapse events and changes to empathic behavior. Further, there is significant overlap in the underlying neural substrates of these complex behaviors, including the insula, paraventricular nucleus of thalamus (PVT), and the paraventricular nucleus of the hypothalamus (PVN). In this review, we will discuss our current understanding of the interplay between empathic behaviors and SUD. We will also examine the underlying neurobiology that may regulate this interaction, focusing specifically on the insula, PVT, and PVN. Finally, we discuss the biologic and therapeutic importance of taking empathic processes into consideration when discussing SUD.

Keywords: Addiction; Empathy; Insula; Paraventricular nucleus of the hypothalamus (PVN); Paraventricular nucleus of the thalamus (PVT); Perception action model (PAM); Self-administration (SA); Targeted helping.

Figure 1.. Rats undergoing heroin abstinence demonstrate diminished targeted helping.

The experimental timeline depicts that male Sprague Dawley Observer rats (n=4/group) underwent intravenous jugular catheter surgery, 15 days of self-administration (SA) of either heroin or saline, 7 days of abstinence in their home cages with their Target cagemate, and then performed the three-chamber targeted helping task (as described in Cox and Reichel, 2020; Cox et al., 2022a; 2022b). A-B). Total nose pokes (A) and infusions (B) per session were recorded for each day of SA. Rats given the opportunity to SA heroin had significantly more total nose pokes and infusions compared to the saline control group (self-administration day X group interaction, F(14,196)=8.77, p<0.0001, post hoc Holm’s Sidak, P<0.05) and a greater number of infusions (self-administration day X group interaction, F(14,196)=6.46, p<0.0001, post hoc Holm’s Sidak, P<0.05) compared to saline control Observers. C). Following abstinence, Observers underwent 10 days of testing in the targeted helping task. Chain pull release latency was recorded and a difference score between the first and last days of testing were calculated as: day 1 latency - day 10 latency. Saline Observers demonstrated significantly higher difference scores versus the heroin group, indicating only the saline group had a change in latency over time [t(6)=2.39, p<0.027]. These data have not been published elsewhere. *p<0.05, significant difference between saline and heroin.

Figure 2.. Oxytocin neurons in the PVN are active during targeted helping.

Male Sprague Dawley rats (n=3–6/group) were trained to release a distressed conspecific in a three chamber targeted helping task. On test day, animals either remained in their home cage (Controls, “Con”) or performed the targeted helping task (Observers, “Obs”). Ninety minutes following the targeted helping session, rats were transcardinally perfused, and their brains were processed as previously described (Cox et al., 2022b). A) The average number of Oxy+ cells per animal within the PVN did not differ between the two groups [t(7)=0.52, p>0.05)]. B) However, the number of Fos+ cells in the PVN of Obs animals was significantly higher [t(7)=3.45, p<0.005)]. C) Further, the number of Oxy+/Fos+ cells, an indication of active Oxy neurons, within the PVN, were also higher in the Obs groups [t(7)=2.9, p<0.0114)], suggesting a higher level of activity within the PVN of animals that performed the task.. D) Representative images of immunohistochemical detection of oxytocin and c-fos, as well as an overlay indicating Oxy+/Fos+ cells. These data have not been published elsewhere. *p<0.05, **p<0.01, significant difference between control and observers