Functional Domains of Substance Use and their Implications to Trauma: A Systematic Review of Neuroimaging Studies.

Substance use disorder (SUD) is a significant health problem, and trauma exposure is a known risk factor for the escalation of substance use. However, the shared neural mechanisms through which trauma is associated with substance use are still unknown. Therefore, we systematically review neuroimaging studies focusing on three domains that may contribute to the overlapping mechanisms of SUD and trauma-reward salience, negative emotionality, and inhibition. Using PRISMA guidelines, we identified 45 studies utilizing tasks measuring these domains in alcohol, tobacco, and cannabis use groups. Greater reward, lesser regulation of inhibitory processes, and mixed findings of negative emotionality processes in individuals who use substances versus controls were found. Specifically, greater orbitofrontal cortex, ventral tegmental area, striatum, amygdala, and hippocampal activation was found in response to reward-related tasks, and reduced activation was found in the inferior frontal gyrus and hippocampus in response to inhibition-related tasks. Importantly, no studies in trauma-exposed individuals met our review criteria. Future studies examining the role of trauma-related factors are needed, and more studies should explore inhibition- and negative-emotionality domains in individuals who use substances to uncover clinically significant alterations in these domains that place an individual at greater risk for developing a SUD.

Serotonin Signaling in Hippocampus during Initial Cocaine Abstinence Drives Persistent Drug Seeking.

The initiation of abstinence after chronic drug self-administration is stressful. Cocaine-seeking behavior on the first day of the absence of the expected drug (Extinction Day 1, ED1) is reduced by blocking 5-HT signaling in dorsal hippocampal cornu ammonis 1 (CA1) in both male and female rats. We hypothesized that the experience of ED1 can substantially influence later relapse behavior and that dorsal raphe (DR) serotonin (5-HT) input to CA1 may be involved. We inhibited 5-HT1A/1B receptors (WAY-100635 plus GR-127935), or DR input (chemogenetics), in CA1 on ED1 to test the role of this pathway on cocaine-seeking persistence 2 weeks later. We also inhibited 5-HT1A or 5-HT1B receptors in CA1 during conditioned place preference (CPP) for cocaine, to examine mechanisms involved in the persistent effects of ED1 manipulations. Inhibition of DR inputs, or 5-HT1A/1B signaling, in CA1 decreased drug seeking on ED1 and decreased cocaine seeking 2 weeks later revealing that 5-HT signaling in CA1 during ED1 contributes to persistent drug seeking during abstinence. In addition, 5-HT1B antagonism alone transiently decreased drug-associated memory performance when given prior to a CPP test, whereas similar antagonism of 5-HT1A alone had no such effect but blocked CPP retrieval on a test 24 h later. These CPP findings are consistent with prior work showing that DR inputs to CA1 augment recall of the drug-associated context and drug seeking via 5-HT1B receptors and prevent consolidation of the updated nondrug context via 5-HT1A receptors. Thus, treatments that modulate 5-HT-dependent memory mechanisms in CA1 during initial abstinence may facilitate later maintenance of abstinence.

The role of social connection in opioid use disorder treatment engagement.

OBJECTIVE: Medications for opioid use disorder (OUD or MOUD) treatment combining pharmacotherapy with psychosocial support are effective for managing OUD. However, treatment engagement remains a challenge, with retention rates ∼30%-50%. Although social connection has been identified as important to recovery, it remains unclear whether and how social factors can bolster participation in treatment. METHOD: Individuals receiving MOUD at three outpatient treatment programs (N = 82) and healthy community controls (N = 62) completed validated measures assessing social connection including (a) size, diversity, and embeddedness of social networks; (b) perceived social support and criticism within familial relationships; and (c) subjective social status. For those receiving MOUD, we also examined how aspects of social connection related to opioid (re)use and treatment engagement (medication adherence, group, and individual meeting attendance) assessed over ∼8 weeks/person. RESULTS: Compared to controls, individuals receiving MOUD had smaller and less diverse and embedded social networks (Cohen's d > 0.4), and despite similar levels of perceived social support (d = 0.02), reported higher levels of social criticism (d = 0.6) and lower subjective social status (d = 0.5). Within the MOUD group, higher social network indices correlated specifically with higher therapeutic group attendance (Rs > 0.30), but not medication adherence, while higher levels of perceived criticism correlated with more frequent opioid use (R = 0.23). Results were mostly robust to control for sociodemographic variables, psychological distress/COVID-19, and treatment duration, but differed by MOUD type/program. CONCLUSIONS: These findings highlight the potential importance of assessing an individual's social capital, promoting positive social connection, and continuing to assess the implementation and value of psychosocial support in MOUD treatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).