Neurosteroid Influences on Sensitivity to Ethanol

This review will highlight a variety of mechanisms by which neurosteroids affect sensitivity to ethanol, including physiological states associated with activity of the hypothalamic–pituitary–adrenal (HPA) and hypothalamic–pituitary–gonadal (HPG) axes, and the effects of chronic exposure to ethanol, in addition to behavioral implications. To date, γ-aminobutyric acid (GABAA) receptor mechanisms are a major focus of the modulation of ethanol effects by neuroactive steroids. While NMDA receptor mechanisms are gaining prominence in the literature, these complex data would be best discussed separately. Accordingly, GABAA receptor mechanisms are emphasized in this review with brief mention of some NMDA receptor mechanisms to point out contrasting neuroactive steroid pharmacology. Overall, the data suggest that neurosteroids are virtually ubiquitous modulators of inhibitory neurotransmission. Neurosteroids appear to affect sensitivity to ethanol in specific brain regions and, consequently, specific behavioral tests, possibly related to the efficacy and potency of ethanol to potentiate the release of GABA and increase neurosteroid concentrations. Although direct interaction of ethanol and neuroactive steroids at common receptor binding sites has been suggested in some studies, this proposition is still controversial. It is currently difficult to assign a specific mechanism by which neuroactive steroids could modulate the effects of ethanol in particular behavioral tasks

Bupropion Attenuates Methamphetamine Self-Administration in Adult Male Rats

Bupropion is a promising candidate medication for methamphetamine use disorder. As such, we used a preclinical model of drug-taking to determine the effects of bupropion on the reinforcing effects of methamphetamine (0.025, 0.05 or 0.1 mg/kg/infusion). Specificity was determined by investigating the effects of bupropion on responding maintained by sucrose. In the selfadministration study, rats were surgically prepared with indwelling jugular catheters and trained to self-administer methamphetamine under an FR5 schedule. A separate group of rats was trained to press a lever for sucrose. Once responding stabilized, rats were pretreated with bupropion (0, 10, 30 and 60 mg/kg IP) 5 min before chamber placement in a unique testing order. Following acute testing, rats were then repeatedly pretreated with 30 and 60 mg/kg bupropion. Acute treatments of bupropion dose dependently reduced drug intake for 0.025 to 0.1 mg/kg methamphetamine; sucrose deliveries were only reduced with the high bupropion dose. Repeated exposure to 60 mg/ kg bupropion before the session resulted in a consistent decrease in methamphetamine intake (0.05 and 0.1 mg/kg) and sucrose deliveries. Considered together, this pattern of findings demonstrates that bupropion decreases responding for methamphetamine, but the effects are only somewhat specific

Trauma in Veterans with Substance Use Disorder: Similar Treatment Need among Urban and Rural Residents

Purpose: The objective of this study is to determine whether rural residence is associated with trauma exposure or posttraumatic stress disorder symptoms among military veterans seeking treatment for substance use disorder (SUD) through the Department of Veterans Affairs (VA). Delivering mental health services to veterans in rural areas is a challenge, so identifying differences in the causes and outcomes of trauma exposure would assist in effectively targeting service delivery. Methods: Veterans (N = 196) entering SUD treatment at 3 Midwestern VA treatment centers were designated as either urban or rural, based on rural-urban commuting area (RUCA) codes. The veterans completed the Life Events Checklist, the Posttraumatic Stress Disorder Checklist, and the Addiction Severity Index’s psychiatric status subscale. Hypothesized relationships between rural-urban residence and both trauma exposure and symptomology were tested using independent samples t tests, chi-square tests, and ordinary least squares regression. Findings: The range of traumatic experiences was similar between rural and urban veterans, and rural-urban residence was not significantly associated with the overall array of traumas experienced or the symptom measures’ overall scores or subscores. Of 17 possible traumatic lifetime experiences, rural veterans differed from urban veterans on only 2, reporting significantly lower rates of transportation accidents and unwanted sexual experiences. Conclusions: In both the causes of trauma and the need for treatment, veterans residing in rural areas differ little from their urban counterparts

DSM-5 criteria for substance use disorders: recommendations and rationale.

Since DSM-IV was published in 1994, its approach to substance use disorders has come under scrutiny. Strengths were identified (notably, reliability and validity of dependence), but concerns have also arisen. The DSM-5 Substance-Related Disorders Work Group considered these issues and recommended revisions for DSM-5. General concerns included whether to retain the division into two main disorders (dependence and abuse), whether substance use disorder criteria should be added or removed, and whether an appropriate substance use disorder severity indicator could be identified. Specific issues included possible addition of withdrawal syndromes for several substances, alignment of nicotine criteria with those for other substances, addition of biomarkers, and inclusion of nonsubstance, behavioral addictions.This article presents the major issues and evidence considered by the work group, which included literature reviews and extensive new data analyses. The work group recommendations for DSM-5 revisions included combining abuse and dependence criteria into a single substance use disorder based on consistent findings from over 200,000 study participants, dropping legal problems and adding craving as criteria, adding cannabis and caffeine withdrawal syndromes, aligning tobacco use disorder criteria with other substance use disorders, and moving gambling disorders to the chapter formerly reserved for substance-related disorders. The proposed changes overcome many problems, while further studies will be needed to address issues for which less data were available

Bupropion and Nicotine Patch as Smoking Cessation Aids in Alcoholics

This is a double blind placebo controlled study of sustained release bupropion as a smoking cessation aid in alcoholics undergoing treatment for their alcoholism. Participants (N=58) were enrolled within one week of entry into alcohol treatment from community and Veterans Affairs Substance Use Disorder programs. All participants received nicotine patch and were invited to attend a smoking cessation lecture and group. Cigarette smoking and alcohol outcomes were measured at six months. Bupropion when added to nicotine patch did not improve smoking outcomes. One-third of participants on bupropion reported discontinuing the drug during weeks 1-4. Participants reported cigarette outcomes with nicotine patch which are similar to those seen in the general population. All study participants significantly reduced cigarette use. Co-morbid affective disorder or antipersonality disorder did not affect outcomes. Alcohol outcomes were improved in those who discontinued cigarettes

Longitudinal Evaluation of Fatty Acid Metabolism in Normal and Spontaneously Hypertensive Rat Hearts with Dynamic MicroSPECT Imaging

The goal of this project is to develop radionuclide molecular imaging technologies using a clinical pinhole SPECT/CT scanner to quantify changes in cardiac metabolism using the spontaneously hypertensive rat (SHR) as a model of hypertensive-related pathophysiology. This paper quantitatively compares fatty acid metabolism in hearts of SHR and Wistar-Kyoto normal rats as a function of age and thereby tracks physiological changes associated with the onset and progression of heart failure in the SHR model. The fatty acid analog, 123I-labeled BMIPP, was used in longitudinal metabolic pinhole SPECT imaging studies performed every seven months for 21 months. The uniqueness of this project is the development of techniques for estimating the blood input function from projection data acquired by a slowly rotating camera that is imaging fast circulation and the quantification of the kinetics of 123I-BMIPP by fitting compartmental models to the blood and tissue time-activity curves

Intensive Referral of Veterans to Mutual-Help Groups: A Mixed-Methods Implementation Evaluation

Community-based support group participation protects against substance use disorder (SUD) relapse, but referrals during treatment are inconsistently delivered and may not acknowledge barriers facing rural patients. This formative evaluation of a rural intensive referral intervention (RAIR) to community-based support groups for veterans seeking SUD treatment surveyed patients (N = 145) and surveyed and interviewed treatment staff (N = 28). Patients and staff did not differ significantly on quantitative ratings of the helpfulness of, or satisfaction with, seven RAIR components, but staff did not deliver the intervention consistently or as designed, citing two themes: lack of commitment and lack of resources

Intensive Referral to Mutual-Help Groups: A Field Trial of Adaptations for Rural Veterans

Objective: A multisite field trial testing whether improved outcomes associated with intensive referral to mutual help groups (MHGs) could be maintained after the intervention was adapted for the circumstances and needs of rural veterans in treatment for substance use disorder (SUD). Methods: In three Veterans Affairs treatment programs in the Midwest, patients (N = 195) received standard referral (SR) or rural-adapted intensive referral (RAIR) and were measured at baseline and 6-month follow-up. Results: Both groups reported significant improvement at 6 months but no significant differences between SR and RAIR groups in MHG participation, substance use, addiction severity, and posttraumatic stress symptoms. Inconsistent delivery of the intervention resulted in only one-third of the RAIR group receiving the full three sessions, but this group reported significantly greater 6-month abstinence from alcohol than those receiving no sessions. Conclusion: Further research should explore implementation problems and determine whether consistent delivery of the intervention enhances 12-step facilitation. Practice implications: The addition of rural-specific elements to the original intensive referral intervention has not been shown to increase its effectiveness among rural veterans