Background: Rodent models of high alcohol drinking offer opportunities to better understand factors for alcohol use disorders (AUD) and test potential treatments. Selective breeding was carried out to create 2 unique High Drinking in the Dark (HDID-1, HDID-2) mouse lines that represent models of genetic risk for binge-like drinking. A number of studies have indicated that neuroimmune genes are important for regulation of alcohol drinking. We tested whether compounds shown to reduce drinking in other models also reduce alcohol intake in these unique genetic lines.Methods: We report tests of gabapentin, tesaglitazar, fenofibrate, caffeic acid phenethyl ester (CAPE), ibrutinib, and rolipram. Although these compounds have different mechanisms of action, they have all been shown to reduce inflammatory responses. We evaluated effects of these compounds on alcohol intake. In order to facilitate comparison with previously published findings for some compounds, we employed similar schedules that were previously used for that compound.Results: Gabapentin increased ethanol (EtOH) binge-like alcohol drinking in female HDID-1 and HS/NPT mice. Tesaglitazar and fenofibrate did not alter 2-bottle choice (2BC) drinking in male HDID-1 or HS/NPT mice. However, tesaglitazar had no effect on DID EtOH intake but reduced blood alcohol levels (BAL), and fenofibrate increased DID intake with no effects on BAL. CAPE had no effect on EtOH intake. Ibrutinib reduced intake in female HDID-1 in initial testing, but did not reduce intake in a second week of testing. Rolipram reduced DID intake and BALs in male and female HDID-1, HDID-2, and HS/NPT mice.Conclusions: A number of compounds shown to reduce EtOH drinking in other models, and genotypes are not effective in HDID mice or their genetically heterogeneous founders, HS/NPT. The most promising compound was the PDE4 inhibitor, rolipram. These results highlight the importance of assessing generalizability when rigorously testing compounds for therapeutic development.

Recent research suggests a role for the appetite hormone leptin in cigarette smoking. This study examined patterns of change in leptin in response to stress and associations with craving during the initial phase of a quit attempt. Thirty-six smokers (average age ± SEM, 33.4 ± 2.4) interested in smoking cessation set a quit day and were required to be abstinent for 24 hours. After, they completed a laboratory session including public speaking and cognitive challenges, and attended 4 weekly post-cessation assessments. Blood samples and self-report measures were collected throughout the laboratory session. The results indicated that leptin levels significantly increased following exposure to acute stress. We also found positive correlations between leptin and craving for cigarettes. No differences were observed in leptin levels between smokers who maintained abstinence for 4 weeks and those who relapsed during this period. These findings suggest that leptin levels may change in response to stress and that leptin could be a useful marker of craving for smoking.

The NAVIGATE program was developed for the Recovery After Initial Schizophrenia Episode-Early Treatment Program (RAISE-ETP) study, which compared NAVIGATE to usual Community Care in a cluster randomized design involving 34 sites and 404 patients. This article describes the approach to training and implementing the NAVIGATE program at the 17 sites (including 134 practitioners) randomized to provide it, and to evaluating the fidelity of service delivery to the NAVIGATE model. Fidelity was evaluated to five different components of the program, all of which were standardized in manuals in advance of implementation. The components included four interventions (Individualized Resiliency Training, Family Education Program, Supported Employment and Education, Personalized Medication Management) and the overall organization (staffing and structure) of the NAVIGATE team. Most of the sites demonstrated acceptable or higher levels of fidelity in their implementation of the four interventions and the organization of the program, with all 17 sites demonstrating at least acceptable overall fidelity to the NAVIGATE program. The results indicate that the NAVIGATE program can be implemented with good fidelity to the treatment model in a diverse array of community mental health care settings serving persons with a first episode psychosis.

The prairie vole (Microtus ochrogaster) is an extensively studied model for understanding the neural mechanisms underlying social affiliations and pair bonds. With clearly observed face and construct validity, this species offers translational insights into mechanisms involved in intimate relationships in humans. Moreover, the prairie vole model promises to advance our understanding – as well as allow for predictions – of the effects of extraneous factors (not normally encountered in nature) on such relationships. This mini review describes some of the neurobiological mechanisms regulating social affiliation in prairie voles, followed by an overview of the effects of alcohol and other drugs of abuse on formation and maintenance of pair-bonds. Based on available literature, we demonstrate that the effects of such extraneous factors on formation and maintenance of pair-bonds are sex-dependent, as well as dependent on the specific nature of the addictive drug. In turn, the lack of similarities in effects of different addictive substances on pair-bond formation suggests that these substances engage different neurocircuits that may or may not overlap with neurocircuits involved in various social behaviors. This lack of consistency of effects across studied drugs of abuse indicates the need to further examine the effects of individual drugs on affiliative behaviors. We highlight the deficiencies in this field of research, particularly the sparsity of studies on effects of drugs of abuse on the maintenance of established bonds. Future investigations in this field could help design strategies to help afflicted individuals.