Author ORCID Identifier
https://orcid.org/0000-0002-7223-7117
Date Available
10-6-2026
Year of Publication
2025
Document Type
Doctoral Dissertation
Degree Name
Doctor of Philosophy (PhD)
College
Arts and Sciences
Department/School/Program
Psychology
Faculty
Dr. Michael Bardo
Abstract
The role of social influences regarding addiction-like behaviors have been shown to have both positive and negative impacts. Having a positive and wide supportive social network increases the longevity of abstinence in humans (Kelly et al., 2014; Mercer et al., 2021). Rodents that have access to enriching environments that include social peers self-administer less drug and drug seek less compared to rodents in isolation (Bardo et al., 2001; Garcia & Cain, 2021; Ranaldi et al., 2011). On the other hand, social factors can increase the likelihood of relapsing (de Wit & Sayette, 2018; Yates, 2023). In preclinical models, social peers have been shown to serve as discriminative cues that lead to increased drug taking and seeking behaviors (Smith, 2012; Humburg & Bardo, 2023).
The purpose of this study was to determine how differential social rearing may affect peer-induced renewal of fentanyl seeking behavior in rats. To examine this, an ABA renewal design was used in which differentially reared rats were first trained to self-administer fentanyl with a peer (context A) and then lever pressing was extinguished without the peer (context B). When the peer was reintroduced (context A), lever pressing was renewed, which is thought to represent drug seeking.
Adolescent male and female Sprague-Dawley rats (postnatal day 21) were reared in a social condition (SC) or isolated condition (IC) into adulthood. These housing conditions were kept the same for the whole duration of the experiment. Beginning at 50 days of age, rats were briefly trained to lever press for food reinforcement followed by surgical implantation under anesthesia of a chronic indwelling catheter for drug delivery. After rats recovered from surgery, a dual-compartment apparatus was used to train rats to self-administer fentanyl (2.5 ug/kg/inf) in one compartment while a passive (non-self-administering) peer was placed in the adjacent compartment separated by a wire screen partition. Fentanyl self-administration was acquired using an incremental fixed ratio 5 (FR5) schedule of reinforcement in the presence of a same age/sex peer for 21 1-hr sessions (context A). The peers were kept the same for each rat across these training sessions. Next, rats underwent extinction training (no fentanyl) with either their peer removed (context B) or present (context A). For the renewal test, both context A (peer) and B (no peer) conditions were tested to assess renewal of fentanyl seeking. Following the last renewal test, all rats were perfused 30 minutes after the test session was completed and brains were taking for immunohistochemical analysis focusing on the nucleus accumbens (NAc) and paraventricular nucleus (PVN). NAc c-Fos activation was assessed in both the core and shell subregions. Oxytocin (OT) and c-Fos activation was assessed within the PVN.
SC and IC rats showed similar rates of fentanyl acquisition in context A. All groups extinguished lever pressing with ABA rats showing a more complete extinction than AAA rats. There were no differences in extinction between SC and IC rats. On the renewal test, ABA rats renewed their fentanyl seeking when reintroduced to their context A peer compared to the AAA rats. More importantly, although IC rats had overall higher responding than SC rats, there was no significant difference between SC and IC rats in the strength of renewal. SC rats had overall lower density of c-Fos+ cells within the NAc core and shell compared to IC rats, regardless of context or peer conditions. Regardless of the test and context conditions, there is a significant difference in density of c-Fos+ cells between the NAc core and shell, with core having more c-Fos+ cells than the shell. Within the PVN, there were no significant differences in density of OT+ cells or OT+/c-Fos+ cells among the different treatment conditions; however, the number of OT+ cells co-labelled with c-Fos+ was extremely low (~5-10%). The density of total c-Fos+ cells in PVN was higher following exposure to the peer test compared to the no peer test in ABA rats, but not in AAA rats regardless of housing condition.
Social housing is able to attenuate arousal of behavior after extinction but is not strong enough to decrease/block renewal of fentanyl seeking. However, these results indicate that peers can serve as potent triggers for relapse, regardless of the social housing environment in which animals are raised. In addition to these findings, social housing leads to an attenuation of neural activity within the NAc which may play a role in the attenuation of behavior. Lastly, rats reintroduced to their drug associated peer after extinction leads to an increase in general c-Fos activity within the PVN, suggesting that other cell types besides OT play a critical role in the renewal of fentanyl seeking triggered by a social peer.
Digital Object Identifier (DOI)
https://doi.org/10.13023/etd.2025.469
Funding Information
National Institute of Health grant R01 DA053070 (Turner, Ortinski, & Bardo)
National Institute on Drug Abuse T32 DA03520 (Rush, Stoops, & Clark)
The Dennis & Sarah McCarty Alcohol & Drug Dissertating Research Award
Recommended Citation
Humburg, Bree A., "THE EFFECTS OF DIFFERENTIAL REARING ON THE SOCIAL RENEWAL OF FENTANYL SEEKING" (2025). Theses and Dissertations--Psychology. 286.
https://uknowledge.uky.edu/psychology_etds/286
