Aspirin May Be a Suitable Prophylaxis for Patients with a History of Venous Thromboembolism Undergoing Total Joint Arthroplasty.

BACKGROUND: In recent years, aspirin has become a popular agent for venous thromboembolism (VTE) prophylaxis following total joint arthroplasty (TJA). Yet patients with a history of VTE are often given more aggressive prophylactic agents because of their increased baseline risk. The purpose of this study was to assess whether aspirin is an effective prophylactic agent in patients with a history of VTE. METHODS: This was a single-institution, retrospective cohort study. The electronic clinical records of 36,333 patients undergoing TJA between 2008 and 2020 were reviewed. Data on demographic characteristics, comorbidities, intraoperative factors, and postoperative complications were collected. A propensity score-matched analysis was performed, as well as a multivariate regression analysis to account for confounders. RESULTS: Of the 36,333 patients undergoing TJA, 1,087 patients (3.0%) had a history of VTE and were not receiving chronic non-aspirin. The risk for subsequent VTE was significantly higher (p = 0.03) in patients with a history of VTE (1.4%) compared with patients without prior VTE (0.9%). However, the incidence of VTE was not significantly lower (p = 0.208) in patients with a history of VTE who received aspirin (0.4%) compared with patients who received other VTE prophylaxis (1.5%). Propensity score matching showed no difference in VTE rates between the 2 groups (2.2% compared with 0.55%; p = 0.372). In a regression analysis accounting for VTE risk, the administration of aspirin was not associated with an increased risk for subsequent VTE (adjusted odds ratio, 0.32 [95% confidence interval, 0.02 to 1.66]; p = 0.274). CONCLUSIONS: Our findings suggest that, although patients with a history of VTE have an increased baseline risk for subsequent VTE, aspirin may be a suitable VTE prophylaxis in this group of patients. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Scaphoid Nonunion: A Review of Surgical Strategies.

The scaphoid is predisposed to nonunion after fracture because of its tenuous blood supply and propensity for delayed diagnosis. Many surgical techniques exist and continue to be developed to treat scaphoid non-unions. However, with variability in patient presentation, differences in nonunion location and type, and multiple bone graft sources and fixation options, selecting a surgical strategy proves a difficult task. The goal of this article is to provide an updated review of surgical strategies used to treat scaphoid nonunions. Particular attention is paid to methods of fixation as well as the ongoing debate over indications for structural and vascularized bone grafting. [Orthopedics. 2022;45(5):e235-e242.].

Surgical Helmets Used During Total Joint Arthroplasty Harbor Common Pathogens: A Cautionary Note.

BACKGROUND: The use of personal-protection surgical helmet/hood systems is now a part of the standard surgical attire during arthroplasty in North America. There are no protocols for the disinfection of these helmets. METHODS: This is a prospective, single-center, observational study. Helmets worn by 44 members of the surgical team and foreheads of 44 corresponding surgical personnel were swabbed at three distinct time points. In addition, 16 helmets were treated with hypochlorite spray to determine if pathogens could be eliminated. Swabs obtained were processed for culture and next-generation sequencing (NGS). RESULTS: Of the 132 helmet samples, 97 (73%) yielded bacteria on culture and 94 (71%) had evidence of bacterial-deoxyribonucleic acid (DNA) on NGS. Of the swabs sent for bacterial identification at the three time points, at least one from each helmet was positive for a pathogen(s). Of the 132 forehead samples, 124 (93%) yielded bacteria on culture and 103 (78%) had evidence of bacterial-DNA on NGS. The most commonly identified organism from helmets was Cutibacterium acnes (86/132) on NGS and Staphylococcus epidermidis (47/132) on culture. The most commonly identified organism from the foreheads of surgical personnel was Cutibacterium acnes (100/132) on NGS and Staphylococcus epidermidis (70/132) on culture. Sanitization of helmets was totally effective; no swabs taken the following morning for culture and NGS identified any bacteria. CONCLUSION: This study demonstrates that surgical helmets worn during orthopedic procedures are contaminated with common pathogens that can potentially cause surgical site infections. The findings of this study should at the minimum compel us to develop protocols for the disinfection of these helmets.

Journey around the Notch: A Systematic Review on the History of ACL Reconstruction in the United States.

The evolution of anterior cruciate ligament (ACL) surgery, seemingly circular at times, informs and provides context for past and current controversies in ACL management. The purpose of this systematic review is to objectively summarize the historical course of ACL reconstruction and repair in the United States over the last 40 years. Femoral tunnel drilling and graft selection have evolved dramatically over the last few decades. An initial focus on restoring ACL anatomy was for a period sacrificed for decreased operative morbidity. However, recent developments in operative techniques aim to restore ACL anatomy while also achieving minimal operative morbidity. Despite this historically iterative process, there remains no perfect choice for the treatment of ACL tears. Continued research on ACL repair, anatomic graft placement, graft choice, and augmentation will help our patients over the next generation.

Volar Plating versus Headless Compression Screw Fixation of Scaphoid Nonunions: A Meta-analysis of Outcomes.

Background Headless compression screw fixation with bone grafting has been the mainstay of treatment for scaphoid nonunion for the past several decades. Recently, locked volar plate fixation has gained popularity as a technique for scaphoid fixation, especially for recalcitrant or secondary nonunions. Purpose The purpose of this meta-analysis was to compare union rates and clinical outcomes between locked volar plate fixation and headless compression screw fixation for the treatment of scaphoid nonunions. Methods A literature search was performed for studies documenting treatment outcomes for scaphoid nonunions from 2000 to 2020. Inclusion criteria consisted of (1) average age > 18 years, (2) primary study using screw fixation, plate fixation, or both, with discrete data reported for each procedure, and (3) average follow-up of at least 3 months. Exclusion criteria consisted of studies with incomplete or missing data on union rates. Data from each study was weighted, combined within treatment groups, and compared across treatment groups using a generalized linear model or binomial distribution. Results Following title and full-text review, 23 articles were included for analysis. Preoperatively, patients treated with plate fixation had significantly longer time from injury to surgery and were more likely to have failed prior surgical intervention. There was no significant difference between union rates at 92 and 94% for screw and plate fixation, respectively. However, plate fixation resulted in longer time to union and lower modified Mayo wrist scores. Conclusion Patients treated with locked volar plate fixation were more likely to be used for recalcitrant or secondary nonunions. There was no statistically significant difference in union rates between screw and plate fixation. The results from this meta-analysis support the select use of locked volar plate fixation for scaphoid nonunion, especially recalcitrant nonunions and those that have failed prior surgical repair.

Polyethylene Glycol Fusion of Nerve Injuries: Review of the Technique and Clinical Applicability.

Traumatic peripheral nerve injuries present a particular challenge to hand surgeons as mechanisms of nerve-healing pose serious limitations to achieving complete functional recovery. The loss of distal axonal segments through Wallerian degeneration results in the loss of neuromuscular junctions and irreversible muscle atrophy. Current methods of repair depend on the outgrowth of proximal nerve fibers following direct end-to-end repair or gap repair techniques. Investigational techniques in nerve repair using polyethylene glycol (PEG) nerve fusion have been shown to bypass Wallerian degeneration by immediately restoring nerve axonal continuity, thus resulting in a rapid and more complete functional recovery. The purpose of this article is to review the current literature surrounding this novel technique for traumatic nerve repair, paying particular attention to the underlying physiology of nerve healing and the current applications of PEG fusion in the laboratory and clinical setting. This article also serves to identify areas of future investigation to further establish validity and feasibility and encourage the translation of PEG fusion into clinical use.

Risk of Gastrointestinal Bleeding With Extended Use of Nonsteroidal Anti-Inflammatory Drug Analgesia After Joint Arthroplasty.

BACKGROUND: Chronic nonsteroidal anti-inflammatory drug (NSAID) use is associated with gastrointestinal bleeding via inhibition of endogenous mucosal protection and platelet aggregation. This study aimed to determine whether extended NSAIDs after joint arthroplasty is associated with increased risk of gastrointestinal bleeding. METHODS: This was a retrospective study examining 28,794 adults who underwent joint arthroplasty by one of 50 surgeons from 2016 to 2018. Episodes of gastrointestinal bleeding within 90 days postoperatively were identified prospectively. Postoperative medications were reported directly by patients with electronic questionnaires. The primary analysis was performed using binary logistic regression. RESULTS: A total of 74 (0.26%) episodes of gastrointestinal bleeding occurred within 90 days (median 8 days) postoperatively. Of 5086 patients with complete data included in the primary analysis, 59.6% had used NSAIDs with median duration of 2 weeks (interquartile range, 0-6 weeks). Patients with gastrointestinal bleeding were significantly older (71.3 vs 67.0 years), required longer hospitalizations (2.1 vs 1.5 days), and more commonly had a history of peptic ulcers (10.8% vs 0.9%). However, there was no positive association between NSAID use and gastrointestinal bleeding. In fact, the odds of gastrointestinal bleeding were lower in patients taking NSAIDs. Gastrointestinal bleeding was associated with anticoagulants, antiplatelet agents, and, to a lesser extent, aspirin. CONCLUSION: NSAIDs were not associated with gastrointestinal bleeding and may be prescribed safely for a majority of patients after joint arthroplasty. The greatest odds of gastrointestinal bleeding occurred in patients with peptic ulcer disease and those who received antiplatelet and anticoagulation agents. Increasing age and bilateral surgery were also associated with gastrointestinal bleeding. LEVEL OF EVIDENCE: Level III.

Low-Dose Aspirin Administered for Venous Thromboembolism Prophylaxis Reduces the Incidence of Heterotopic Ossification in Total Joint Arthroplasty.

BACKGROUND: Heterotopic ossification (HO) is a common complication following total joint arthroplasty (TJA). However, the pathophysiology of HO is not entirely understood. Inflammation may play a significant role in the pathogenesis of HO as nonsteroidal anti-inflammatory drugs are effective in the prevention of HO. The purpose of this study is to examine if aspirin (ASA), when used as venous thromboembolism (VTE) prophylaxis, influenced the rate of HO formation following TJA. METHODS: We queried our longitudinally maintained database to identify all patients who underwent primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) for osteoarthritis between January 2016 and June 2018 with at least 3-month radiographic follow-up. In total, 1238 THAs and 1051 TKAs were included for analysis. Radiographs were reviewed and HO formation graded according to the Brooker classification. Patient demographic and VTE prophylaxis data were collected and reviewed for accuracy. Univariate and multivariate analysis was performed to evaluate the effect of ASA on HO formation. RESULTS: The overall rate of HO was 37.5% after THA and 17.4% after TKA. Patients receiving ASA were less likely to develop HO after THA (34.8% vs 45.5%; P < .001), as well as HO after TKA (13.4% vs 18.4%; P = .047) compared to patients receiving non-ASA VTE prophylaxis. The rate of HO formation trended to be lower, albeit not statistically significantly, in patients receiving low-dose ASA (81 mg) vs high-dose ASA (325 mg). CONCLUSION: Patients undergoing primary TJA receiving ASA for VTE prophylaxis were less likely to develop HO compared to patients who were administered non-ASA VTE prophylaxis.

Dual Mobility and Conventional Bearings Have Comparably Low Dislocation Rates for Anterior-Based Approaches in Total Hip Arthroplasty.

BACKGROUND: Dual mobility (DM) bearings for total hip arthroplasty (THA) have been proposed to reduce the risk of instability in select patients, especially those undergoing revision surgery. The use of DM bearings has not been studied as extensively for use in primary THA. The purpose of this study is to compare outcomes following primary THA with anterior-based approaches between patients receiving DM bearings vs standard bearing hip implants. METHODS: We retrospectively reviewed a consecutive series of patients undergoing primary THA through an anterior-based approach. A 3:1 propensity score match was performed between the standard and DM bearing patients to control for possible risk factors for instability. Functional outcomes, dislocations, and aseptic revisions were identified for each patient. The effect of DM on postoperative outcomes was determined using univariate statistical analyses. RESULTS: In total, 250 DM bearings were compared to 753 standard bearings. We found no difference in dislocation rate between single bearings and DM bearings (0.53% vs 0.4%). There was 1 DM dislocation occurring in a liner with outer diameter of 38 mm. There were no DM dislocations with outer diameter >38 mm. Aseptic revision surgery was more common in DM. This difference was driven by higher incidence of femoral periprosthetic fracture. There were no differences in functional outcomes. CONCLUSION: Dislocation rates are comparably low between DM bearings and standard bearings for THA done using an anterior approach to the hip. Further investigation is needed to determine if specific patient populations may benefit from DM implants for primary THA when an anterior approach to the hip is being used.

Rates of Revision Surgery following In Situ Decompression versus Anterior Transposition for the Treatment of Idiopathic Cubital Tunnel Syndrome.

Objective The current understanding of revision rates following surgery for the primary surgical treatment of idiopathic cubital tunnel syndrome (CuTS) remains unclear. The purpose of this study was to describe and compare the rate of revision surgery following in situ decompression (SD) versus anterior transposition (AT) after the surgical treatment of idiopathic CuTS and examine possible predicting variables for revision. Materials and Methods A retrospective cohort study was performed at a single institution by querying records for all CuTS surgeries performed between January 2010 and December 2015. The initial query resulted in 1,967 cases. Exclusion criteria included acute trauma, concurrent unrelated primary elbow procedure, revision surgery, incomplete records, and age younger than 18 or older than 89 years. A total of 1,384 surgeries met criteria for study inclusion. A case-control study was then performed with 39 cases of revision and a group of 76 control cases that did not undergo revision surgery. Bivariate analysis followed by multivariate logistic regression was performed to evaluate predictors of revision. Results Of the 1,384 procedures, 979 were SDs (70.7%) and 405 were ATs (29.3%). Among the 1,384 total procedures, there were 39 primary cubital tunnel surgeries resulting in a revision surgery (2.8%). The revision rate for SD was 3.1% and the revision rate for AT was 2.2%. Predictors of revision were younger age, increased nerve conduction velocity, and decreased duration of symptoms. Conclusion In the surgical treatment of idiopathic CuTS, the overall revision rate is low (2.8%). This study found no significant difference in revision rate between SD and AT, but that risk for revision surgery overall was associated with younger age, increased nerve conduction velocity, and decreased duration of symptoms. Level of Evidence This is a therapeutic, level III study.

Telemedicine Evaluation and Techniques in Hand Surgery.

The demand for telemedicine has been increasing over the past several years with the growth of technology and digital connectivity in our daily lives. With the impact of the global coronavirus disease 2019 pandemic, telemedicine implementation has become a necessity for many specialties because social distancing measures have greatly affected access to routine medical care. This article presents a detailed and systematic approach to conducting a hand physical examination during a video telemedicine encounter. Although the telemedicine physical examination has limitations, most components of the normal physical examination can be completed remotely with a systematic approach. We enumerate modifications to maximize examination remotely and present considerations for improved delivery of telemedicine care. These methods may be beneficial to providers incorporating telemedicine into their practice.

Popliteal Cysts: A Systematic Review of Nonoperative and Operative Treatment.

BACKGROUND: Treatment methods for popliteal cysts have varied over the past several decades and have posed challenges to providers as recurrences were frequent. With greater understanding of relevant anatomy, both operative and nonoperative treatment methods have evolved to appropriately target relevant pathology and improve outcomes. The purposes of this review were to outline the evolution of treatment methods and to qualitatively summarize clinical outcomes. METHODS: We performed a systematic review on treatments for popliteal cysts to include publications from 1970 to 2019. Other inclusion criteria consisted of studies with ≥10 patients enrolled, studies with a patient age of ≥16 years, studies with an adequate description of the treatment technique, and studies with a Level of Evidence of IV or higher. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and literature quality was assessed using a modified Coleman methodology score. RESULTS: Thirty studies met inclusion criteria in this review. Nine studies discussed nonoperative treatment, and 21 studies discussed operative treatment. Eight of the 9 nonoperative treatment studies utilized corticosteroid injections. The most recent studies have advocated for ultrasound-guided intracystic injection with possible cyst fenestration. Most operative studies utilized an arthroscopic approach to enlarge the communication with the joint space. However, alternative treatment techniques are still utilized. CONCLUSIONS: The current literature on the treatment of popliteal cysts indicates that intracystic corticosteroid injection with cyst fenestration is an effective nonoperative treatment method. Arthroscopic surgical procedures with enlargement of the communication have been most widely studied, with positive results; however, further studies are needed to confirm superiority over other treatment methods. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Preconception maternal cocaine self-administration increases the reinforcing efficacy of cocaine in male offspring.

RATIONALE: Although the influence of gestational cocaine exposure on offspring has been the focus of a sustained research effort, the effect of preconception cocaine self-administration by dams on progeny has received far less attention. METHOD: In the current study, adult female rats were allowed to self-administer cocaine 2 h a day for 60 days and then after a 10-day wash out period, bred to naïve males. Maternal behavior was measured in dams until weaning. When male and female progeny reached adulthood, anxiety-like behavior, memory, and cocaine self-administration were assessed in separate cohorts of rats. RESULTS: Despite a total of at least 30 days of cocaine abstinence, the quality of maternal behaviors was negatively affected by previous cocaine exposure as reflected by less time spent with pups as well as an excess of other maladaptive maternal behaviors. Measures of anxiety-like behavior and memory were not affected by maternal cocaine intake in either male or female offspring. In contrast, male, but not female, the progeny of dams exposed to cocaine showed increased reinforcing efficacy of cocaine as measured by cocaine self-administration under a progressive ratio schedule. The fact that cocaine self-administration was influenced only in the male offspring of cocaine-exposed dams argues against this phenotype being linked to altered maternal behavior, although this possibility cannot be ruled out completely. CONCLUSIONS: Collectively, these results indicate that preconception cocaine self-administration by dams results in the relatively selective enhancement of cocaine addiction-like behavior in male offspring.

H3.3 Barcoding of Nucleus Accumbens Transcriptional Activity Identifies Novel Molecular Cascades Associated with Cocaine Self-administration in Mice.

Although numerous epigenetic modifications have been associated with addiction, little work has explored the turnover of histone variants. Uniquely, the H3.3 variant incorporates stably and preferentially into chromatin independently of DNA replication at active sites of transcription and transcription factor binding. Thus, genomic regions associated with H3.3-containing nucleosomes are particularly likely to be involved in plasticity, such as following repeated cocaine exposure. A recently developed mouse line expressing a neuron-specific hemagglutinin (HA)-tagged H3.3 protein was used to track transcriptionally active sites cumulatively across 19 d of cocaine self-administration. RNA-seq and H3.3-HA ChIP-seq analyses were performed on NAcc tissue collected following cocaine or food self-administration in male mice. RNA sequencing revealed five genes upregulated in cocaine relative to food self-administering mice: Fosb, Npas4, Vgf, Nptx2, and Pmepa1, which reflect known and novel cocaine plasticity-associated genes. Subsequent ChIP-seq analysis confirmed increased H3.3 aggregation at four of these five loci, thus validating H3.3 insertion as a marker of enhanced cocaine-induced transcription. Further motif recognition analysis of the ChIP-seq data showed that cocaine-associated differential H3.3 accumulation correlated with the presence of several transcription factor binding motifs, including RBPJ1, EGR1, and SOX4, suggesting that these are potentially important regulators of molecular cascades associated with cocaine-induced neuronal plasticity. Additional ontological analysis revealed differential H3.3 accumulation mainly near genes involved in neuronal differentiation and dendrite formation. These results establish the H3.3-HA transgenic mouse line as a compelling molecular barcoding tool to identify the cumulative effects of long-term environmental perturbations, such as exposure to drugs of abuse.SIGNIFICANCE STATEMENT Histone H3.3 is a core histone variant that is stably incorporated at active sites of transcription. We used a tagged version of H3.3 expressed exclusively in neurons to delineate active transcription sites following extended cocaine self-administration in mice. This approach revealed the cumulative list of genes expressed in response to cocaine taking over the course of several weeks. We combined this technique with RNA sequencing of tissue collected from the same animals 24 h after the last cocaine exposure. Comparing these datasets provided a full picture of genes that respond to chronic cocaine exposure in NAcc neurons. These studies revealed novel transcription factors that are likely involved in cocaine-induced plasticity and addiction-like behaviors.

Ulnar Nerve In Situ Decompression versus Transposition for Idiopathic Cubital Tunnel Syndrome: An Updated Meta-Analysis.

Purpose Evidence for the superiority of in situ simple decompression (SD) versus ulnar nerve transposition (UNT) for cubital tunnel syndrome remains controversial. The purpose of this study was to compare the clinical improvement, complication rate, and revision rate of SD versus UNT using the available evidence. Materials and Methods We performed a literature search of relevant publications using PubMed, SCOPUS, Cochrane Library, and Springer Link. Inclusion criteria included (1) adult patients >18 years of age, (2) idiopathic cubital tunnel syndrome, (3) primary comparison studies including both SD versus UNT with discrete data for each procedure, (4) average follow-up of at least 2 months, and (5) a full English language manuscript available. Odds ratios of improvement, complications, and revision surgery after SD compared with UNT were calculated. Data were analyzed using both fixed and random effects models, and studies were assessed for publication bias and heterogeneity. Results A total of 1,511 articles from 1970 to 2017 were identified before inclusion, and exclusion criteria were applied. Ultimately 17 studies met the inclusion criteria and included 2,154 procedures. Of these, 1,040 were SD, and 1,114 were UNT procedures. Study heterogeneity was low. Odds ratios of clinical improvement and revision surgery with SD versus UNT were not significantly different. The odds ratio of complications with SD versus UNT was 0.449 (95% confidence interval [CI] of 0.290-0.695) and 0.469 (95% CI of 0.297-0.738) for fixed and random effect models, respectively. The difference in complications between SD versus UNT was significant ( P < 0.001). Conclusion There is no statistically significant difference in clinical outcomes or rate of revision surgery between SD versus UNT. However, there were significantly more complications with UNT. The current body of evidence regarding cubital tunnel syndrome lacks prospective, randomized, controlled trials, uniform reporting of indications, and standardized outcome scoring.

Effects of LY466195, a selective kainate receptor antagonist, on ethanol preference and drinking in rats.

There is evidence that variation in the gene encoding a kainate receptor subunit contributes to alcohol dependence risk. Further, there is suggestive evidence that alcohol consumption is mediated, in part, by kainate receptors. In this study, we used a novel kainate receptor antagonist, LY466195, to examine the potential role of kainate receptors in alcohol drinking behavior using a rodent model of voluntary ethanol consumption. Male Sprague Dawley and Long Evans rats were given access to 20% ethanol using the intermittent two-bottle choice paradigm. Following 6 weeks of ethanol consumption, rats were pretreated with an acute dose of LY466195 (0, 4.0 and 10.0mg/kg, i.p.) prior to a two-bottle choice test session. Acute administration of LY466195 did not significantly affect ethanol-drinking behavior in Sprague Dawley rats. In contrast, Long Evans rats pretreated with 10.0mg/kg LY466195 showed a significant reduction in alcohol preference compared to vehicle-treated controls. Decreased alcohol preference in the Long Evans rats was associated with increased water intake and no change in the amount of ethanol consumed. Taken together, these results suggest that systemic administration of a selective kainate receptor antagonist reduces ethanol preference in rats, an effect that could be due to non-specific effects on overall drinking behavior.

Glucagon-Like Peptide-1 Receptor Activation in the Ventral Tegmental Area Decreases the Reinforcing Efficacy of Cocaine.

Cocaine addiction continues to be a significant public health problem for which there are currently no effective FDA-approved treatments. Thus, there is a clear need to identify and develop novel pharmacotherapies for cocaine addiction. Recent evidence indicates that activation of glucagon-like peptide-1 (GLP-1) receptors in the ventral tegmental area (VTA) reduces intake of highly palatable food. As the neural circuits and neurobiological mechanisms underlying drug taking overlap to some degree with those regulating food intake, these findings suggest that activation of central GLP-1 receptors may also attenuate cocaine taking. Here, we show that intra-VTA administration of the GLP-1 receptor agonist exendin-4 (0.05 µg) significantly reduced cocaine, but not sucrose, self-administration in rats. We also demonstrate that cocaine taking is associated with elevated plasma corticosterone levels and that systemic infusion of cocaine activates GLP-1-expressing neurons in the nucleus tractus solitarius (NTS), a hindbrain nucleus that projects monosynaptically to the VTA. To determine the potential mechanisms by which cocaine activates NTS GLP-1-expressing neurons, we microinjected corticosterone (0.5 µg) directly into the hindbrain fourth ventricle. Intraventricular corticosterone attenuated cocaine self-administration and this effect was blocked in animals pretreated with the GLP-1 receptor antagonist exendin-(9-39) (10 µg) in the VTA. Finally, AAV-shRNA-mediated knockdown of VTA GLP-1 receptors was sufficient to augment cocaine self-administration. Taken together, these findings indicate that increased activation of NTS GLP-1-expressing neurons by corticosterone may represent a homeostatic response to cocaine taking, thereby reducing the reinforcing efficacy of cocaine. Therefore, central GLP-1 receptors may represent a novel target for cocaine addiction pharmacotherapies.

Antidepressant-like effects of buprenorphine in rats are strain dependent.

The prevalence of major depressive disorder and the limited efficacy of conventional drug treatments provide significant impetus to develop novel and more rapidly acting antidepressants for individuals with treatment resistant forms of depression. The primary goal of these studies was to ascertain whether buprenorphine (BPN), a medically available drug with mixed effects at opioid receptors, was effective in behavioral tests using the Wistar Kyoto (WKY) rat strain, a rodent model of exaggerated depressive and anxiety behaviors that demonstrates resistance to certain antidepressants. As WKY rats are maintained by different sources, we assessed the behavioral effects of BPN using the modified rat forced swim test (FST) and the emergence test in WKY rat colonies obtained from different vendors. BPN dose-dependently reduced immobility and increased swimming behavior in the FST and reduced emergence latencies in two WKY lines (Charles River (WKY/NCrl) and Harlan laboratories (WKY/NHsd)) that also showed high baseline immobility in the FST. WKY rats from Taconic (WKY/NTac) did not show high baseline immobility in the FST or anxiety as had been previously reported, suggesting a drift in the phenotype of rats from this supplier. Furthermore, BPN did not reduce immobility in the FST or reduce latencies in the emergence test in WKY rats from Taconic. BPN also failed to produce antidepressant-like effects in Wistar and Sprague-Dawley rats. These results indicate a striking strain-selectivity for the effects of BPN, producing antidepressant and anxiolytic-like responses in WKY/NCrl and WKY/NHsd lines but not in the normosensitive control Wistar and Sprague-Dawley strains.