Dopamine D2 receptors in the bed nucleus of the stria terminalis modulate alcohol-related behaviors.

Dysregulation of the dopamine (DA) system is a hallmark of substance abuse disorders, including alcohol use disorder (AUD). Of the DA receptor subtypes, the DA D2 receptors (D2Rs) play a key role in the reinforcing effects of alcohol. D2Rs are expressed in numerous brain regions associated with the regulation of appetitive behaviors. One such region is the bed nucleus of the stria terminalis (BNST), which has been linked to the development and maintenance of AUD. Recently, we identified alcohol withdrawal-related neuroadaptations in the periaqueductal gray/dorsal raphe to BNST DA circuit in male mice. However, the role of D2R-expressing BNST neurons in voluntary alcohol consumption is not well characterized. In this study, we used a CRISPR-Cas9-based viral approach, to selectively reduce the expression of D2Rs in BNST VGAT neurons and interrogated the impact of BNST D2Rs in alcohol-related behaviors. In male mice, reduced D2R expression potentiated the stimulatory effects of alcohol and increased voluntary consumption of 20% w/v alcohol in a two-bottle choice intermittent access paradigm. This effect was not specific to alcohol, as D2R deletion also increased sucrose intake in male mice. Interestingly, cell-specific deletion of BNST D2Rs in female mice did not alter alcohol-related behaviors but lowered the threshold for mechanical pain sensitivity. Collectively, our findings suggest a role for postsynaptic BNST D2Rs in the modulation of sex-specific behavioral responses to alcohol and sucrose.

Evaluation of a Nursing-Focused Training and Education Strategy for a Facility Transitioning to a Level I Pediatric Trauma Center.

Background Increasing numbers of facilities are pursuing verification as pediatric trauma centers. Nurses need effective training to provide optimal care for pediatric trauma patients. This study evaluated the implementation of a nursing-focused education strategy that accompanied the process of opening a pediatric trauma center. Method Training comprised a lecture series, skills stations, and simulation. Participation was recorded. Pre- and post-training surveys were used to evaluate effectiveness. Results Participation in training was high (lectures, n = 185; skills stations, n = 151; simulation, n = 301). Survey responses indicated an increased confidence to treat pediatric trauma patients (2 out of 5 vs. 3 out of 5; p < .001). Nearly half (49.1%) of the nurses found simulations to be the most effective element of training on the post-training survey. Conclusion High participation and improved confidence indicate a feasible and effective training curriculum. Simulation was perceived as the most effective training modality. [J Contin Educ Nurs. 2022;53(9):405-410.].

The impact of intermittent exercise on mouse ethanol drinking and abstinence-associated affective behavior and physiology.

BACKGROUND: Negative emotional states are associated with the initiation and maintenance of alcohol use and drive relapse to drinking during withdrawal and protracted abstinence. Physical exercise is correlated with decreased negative affective symptoms, although a direct relationship between drinking patterns and exercise level has not been fully elucidated. METHODS: We incorporated intermittent running wheel access into a chronic continuous access, two-bottle choice alcohol drinking model in female C57BL/6J mice. Wheel access was granted intermittently once mice established a preference for alcohol over water. After 6 weeks, alcohol was removed (forced abstinence) and mice were given continuous access to unlocked or locked wheels. Negative affect-like behavior, home cage behavior, and metabolic activity were measured during protracted abstinence. RESULTS: Wheel access shifted drinking patterns in the mice, increasing drinking when the wheel was locked, and decreasing drinking when unlocked. Moreover, alcohol preference and consumption were strongly negatively correlated with the amount of running. An assessment of negative affect-like behavior in abstinence via the novelty suppressed feeding and saccharin preference tests (SPT) showed that unlimited wheel access mitigated abstinence-induced latency increases. Mice in abstinence also spent more time sleeping during the active dark cycle than control mice, providing additional evidence for abstinence-induced anhedonia- and depression-like behavior. Furthermore, running wheel access in abstinence decreased dark cycle sleep to comparable alcohol- and wheel-naïve mice. Given the positive impact of exercise and the negative impact of alcohol on metabolic health, we compared metabolic phenotypes of alcohol-abstinent mice with and without wheel access. Wheel access increased energy expenditure, carbon dioxide production, and oxygen consumption, providing a potential metabolic mechanism through which wheel access improves affective state. CONCLUSIONS: This study suggests that including exercise in AUD treatment regimens has the potential to reduce drinking, improve affective state during abstinence and could serve as a non-pharmacological approach to prevent the development of an AUD in high-risk individuals.

Experimental modification of dysfunctional interpretations in individuals with contamination concerns.

BACKGROUND AND OBJECTIVES: Dysfunctional interpretations of intrusive thoughts are implicated in the etiology and maintenance of Obsessive-Compulsive Disorder (OCD). Cognitive Bias Modification training for interpretations (CBM-I) has successfully modified dysfunctional interpretations in the context of several disorders, including OCD. However, research regarding CBM-I's impact on symptom reduction and behavior is mixed, which limits its clinical application. Further, support for the specific efficacy of CBM-I in individuals with contamination concerns is limited. The current study aimed to modify dysfunctional interpretations in individuals with contamination concerns, and examine the effect of the modification on both interpretation bias and performance on a behavioral approach task (BAT). METHODS: Participants (N = 74) completed a word-sentence association task by indicating whether a threatening or benign word was related to an ambiguous scenario. The active condition received feedback designed to reduce maladaptive interpretations; the control condition received random feedback. RESULTS: Findings revealed that the active-but not the control-condition showed a significant decrease in interpretation bias for threat cues. Analyses of behavioral effects indicated that when ceiling effects were accounted for, the active condition completed more BAT steps than the control condition (p = 0.06; d = 0.45). LIMITATIONS: The current study is preliminary and requires replication with a clinical sample. CONCLUSIONS: Completion of the CBM-I was beneficial for reducing dysfunctional interpretations relevant to naturally-occurring contamination concerns and, importantly, this reduction may help those individuals approach feared situations.

Preliminary Evidence for the Enhancement of Self-Conducted Exposures for OCD using Cognitive Bias Modification.

Exposure and Response Prevention (ERP) is the most effective treatment for OCD but it is not accessible to most patients. Attempts to increase the accessibility of ERP via self-directed ERP (sERP) programs such as computerized delivery and bibliotherapy have met with noncompliance, presumably because patients find the exposure exercises unacceptable. Previous research suggests that Cognitive Bias Modification (CBM) interventions may help individuals approach feared situations. The goal of the current study was to test the efficacy of a treatment program for OCD that integrates sERP with CBM. Twenty-two individuals meeting diagnostic criteria for OCD enrolled in our 7-week treatment program. Results suggest that sERP with CBM led to significant reduction of OCD symptoms and functional impairment. Indeed, the magnitude of the effect of this novel treatment, that requires only an initial session with a clinician trained in ERP for OCD, was comparable to that of the gold standard clinician-administered ERP. Moreover, preliminary evidence suggests that CBM interventions targeting interpretation bias may be most effective, whereas those targeting attention and working memory bias may not be so.