Effects of anterior approach to quadratus lumborum block on postoperative cognitive function following hip surgery in older people: a randomized controlled clinical trial.

BACKGROUND: Peripheral nerve block, including the quadratus lumborum block (QLB), has been used for postoperative analgesia in hip surgery. However, the effects of QLB on cognitive function after hip surgery remain unknown. This study aimed to assess the effects of the anterior approach to QLB on postoperative cognitive function in older people undergoing hip surgery. METHODS: Sixty older people who underwent hip surgery from May 2021 to May 2022 were randomly divided into the QLB (n = 30) and control groups (n = 30). The Montreal Cognitive Assessment (MoCA) score (mean ± SD) was measured one day preoperatively and seven and 30 days postoperatively. The frequency (%) of postoperative cognitive dysfunction (POCD) was examined seven and 30 days postoperatively. The visual analog scale (VAS) scores at rest and Bruggrmann comfort scale (BCS) scores [Median (IQR)] 6 h (t1), 12 h (t2), 24 h (t3), and 48 h (t4) after surgery were assessed. The plasma high mobility group box protein 1 (HMGB1) and levels of interleukin-6 (IL-6) (mean ± SD) were evaluated 1 h preoperatively (baseline) and 24 h postoperatively (day 1). The requirement for rescue analgesia [Median (IQR)], time to first off-bed activity (mean ± SD), and adverse effects after surgery were also recorded. RESULTS: Compared with the control group, the frequency of POCD was significantly lower in the QLB group seven days postoperatively (10.7% vs. 34.5%, P = 0.033), but no difference at 30 days postoperatively (3.6% vs. 10.3%, P = 0.319). There was no significant difference in MoCA scores between the two groups at one day preoperatively and 30 days postoperatively. However, the MoCA scores at seven days postoperatively were higher in the QLB group than in the control group (27.4 ± 1.81 vs. 26.4 ± 1.83, P = 0.043). In the QLB group, the VAS scores at t1, t2, and t3 were lower [3(2-4) vs. 4(3-4), P = 0.028; 3(2-3) vs. 4(3-5), P = 0.009; 2(1-3) vs. 2(2-3), P = 0.025], and the BCS scores at t1, t2, and t3 were higher than those in the control group [3(1-3) vs. 1(1-2), P = 0.006; 3(2-3) vs. 2(1-3), P = 0.011; 3(2-4) vs. 2(2-3), P = 0.041]. The patients in the QLB group reported significantly fewer requirements for rescue analgesia [0(0-1) vs. 1(0-2), P = 0.014]. The plasma levels of HMGB1 and IL-6 at 24 h postoperatively in the QLB group were significantly lower than in the control group (749.0 ± 185.7 vs. 842.1 ± 157.9, P = 0.046; 24.8 ± 8.1 vs. 31.9 ± 5.5, P < 0.001). The time to first off-bed activity from the end of surgery was shorter in the QLB group (25.3 ± 5.3 vs. 29.7 ± 6.9, P = 0.009). There was no significant difference in the incidence of postoperative complications between the two groups. CONCLUSIONS: Anterior QLB given to older people undergoing hip surgery could promote early postoperative cognitive function recovery, provide adequate postoperative analgesia, and inhibit the release of inflammatory factors. TRIAL REGISTRATION: Chictr.org.cn identifier ChiCTR2000040724 (Date of registry: 08/12/2020, prospectively registered).

Electronic Vaporization of Nicotine Salt or Freebase produces differential effects on metabolism, neuronal activity and behavior in male and female C57BL/6J mice.

The use of Electronic Nicotine Delivery Systems (ENDS) is increasing in prevalence and popularity. ENDS are a rapidly evolving technology as devices and e-liquid formulations adapt to policy restrictions and market demand To identify the impacts of nicotine formulation and concentration, we exposed female and male C57BL/6J mice to passive electronic vaporization of different nicotine formulations (freebase or salt) and concentrations (1% or 3%) and measured serum nicotine metabolite levels, brain activity by cFos expression, and anxiety-like and motivated behavior using the novelty suppressed feeding test. We found that the 3% freebase nicotine vapor group displayed significantly higher serum nicotine levels than either 1% or 3% nicotine salt formulations, and female mice displayed higher serum nicotine and cotinine levels compared to males. Central amygdala (CeA) activity was significantly elevated in male mice following nicotine vapor exposure, but the increase was not significantly different between nicotine vapor groups. CeA activity in female mice was unaffected. In contrast increased activity in the ventral tegmental area (VTA) was only observed in female mice exposed to 3% nicotine freebase and specifically in the dopaminergic population. Anxiety-like behavior in female mice was relatively unaffected by nicotine vapor exposure, however male mice displayed increased anxiety-like behavior and reduced motivation to feed after vapor exposure, specifically in the 3% freebase group. These results identify important sex differences in the impact of nicotine formulation and concentration on nicotine metabolism, brain region-specific activity and anxiety-like behavior, which may have significant relevance for different consequences of vaping in men and women.

Sex Differences in the Impact of Electronic Nicotine Vapor on Corticotropin-Releasing Factor Receptor 1 Neurons in the Mouse Ventral Tegmental Area.

Nicotine engages dopamine neurons in the ventral tegmental area (VTA) to encode reward and drive the development of nicotine addiction, however how nicotine alters a stress associated VTA population remains unclear. Here, we used male and female CRF1-GFP mice and nicotine vapor exposure to examine the effects of nicotine in VTA corticotropin-releasing factor receptor 1 (CRF1) neurons. We use immunohistochemistry and electrophysiology to examine neuronal activity, excitability, and inhibitory signaling. We found that VTA CRF1 neurons are mainly dopaminergic and project to the nucleus accumbens (NAc; VTA-NAcCRF1 neurons). VTA-NAcCRF1 neurons show greater phasic inhibition in naive females and greater focal nicotine-induced increases in firing in naive males. Following acute nicotine vapor exposure, phasic inhibition was not altered, but focal nicotine-induced tonic inhibition was enhanced in females and diminished in males. Acute nicotine vapor exposure did not affect firing in VTA-NAcCRF1 neurons, but females showed lower baseline firing and higher focal nicotine-induced firing. Activity (cFos) was increased in the CRF1 dopaminergic VTA population in both sexes, but with greater increases in females. Following chronic nicotine vapor exposure, both sexes displayed reduced basal phasic inhibition and the sex difference in tonic inhibition following acute vapor exposure was no longer observed. Additionally, activity of the CRF1 dopaminergic VTA population was no longer elevated in either sex. These findings reveal sex-dependent and exposure-dependent changes in mesolimbic VTA-NAc CRF1 neuronal activity, inhibitory signaling, and nicotine sensitivity following nicotine vapor exposure. These changes potentially contribute to nicotine-dependent behaviors and the intersection between stress, anxiety, and addiction.SIGNIFICANCE STATEMENT Nicotine is known to engage reward systems in the brain historically centering the neurotransmitter dopamine however, how nicotine impacts other neurons in the reward pathway is less clear. The current study investigates the impact of acute and chronic electronic nicotine vapor exposure in a genetically-defined cell population containing the stress receptor corticotropin-releasing factor 1 (CRF1) that is located in the reward circuitry. This study employs functional measures of neuronal activity and identifies important sex differences in nicotine's effects across time and exposure.

Effect of different acupuncture and moxibustion methods on functional dyspepsia caused by sequelae of COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: Functional dyspepsia (FD) is a group of diseases that cannot be explained after routine clinical examination, and is characterized by postprandial fullness, early satiety, and upper abdominal pain or burning. According to the statistics, FD continues to become one of the high-risk sequelae of coronavirus disease 2019 (COVID-19), affecting patients' quality of life, increasing psychological burden and increasing economic costs. However, its optimal treatment is still an urgent problem. A large number of studies have shown that acupuncture and moxibustion is effective and safe in the treatment of FD caused by sequelae of COVID-19, which is of research value. Therefore, based on the current literatures, the effectiveness and safety of different acupuncture and moxibustion methods were systematically evaluated to provide possible alternative therapy on FD. METHODS: Studies search for eligible randomized controlled trials that use different acupuncture and moxibustion methods as the sole treatment on FD and their data extraction will be done by 2 researchers. In case of disagreement, a third researcher will be introduced for arbitration. Mean difference or relative risk with fixed or random effect model in terms of 95% confidence interval will be adopted for the data synthesis. To evaluate the risk of bias, the Cochrane risk of bias assessment tool will be utilized. The sensitivity or subgroup analysis will also be conducted when meeting high heterogeneity (I2 > 50%). RESULTS: This meta-analysis will provide an authentic synthesis of different acupuncture and moxibustion methods on FD caused by sequelae of COVID-19. CONCLUSION: This meta-analysis will evaluate the effect of acupuncture and moxibustion on FD caused by sequelae of COVID-19, providing evidence as to the treatment in these patients.

Acupuncturing of myofascial pain trigger points for the treatment of knee osteoarthritis: A systematic review and meta-analysis.

BACKGROUND: Osteoarthritis of the knee is one of the major disorders leading to social dysfunction, economic loss and social development. This study was conducted to systematically evaluate the efficacy and safety effectiveness of acupuncture inactivation of myofascial pain trigger points in the treatment of osteoarthritis of the knee. METHODS: Randomized Controlled Trials (RCTs) on the treatment of knee pain were searched by computer from PubMed, The Cochrane Library, China journal full-text database (CNKI), Chinese biomedical literature database (CBM), China academic journal database (Wanfang Data) databases from the date of creation to December 2021, and the data were analyzed by Reman 5.3 software for data analysis. RESULTS: A total of 724 patients from 9 RCTs were finally included, and the results of meta-analysis showed that the acupuncture myofascial pain trigger point group was better than the control group in terms of total effective rate, cure rate, VAS score, Lysholm score, and WOMAC score. CONCLUSION: The efficacy and safety of acupuncturing myofascial pain trigger points in the treatment of knee osteoarthritis is positive, but due to the limited number of literature included in this study and the low quality of the included literature, there is still a need for high-quality and large sample size RCTs for the analysis of this treatment option.

Imaging Findings for Identifying and Evaluating Complications After Lung Transplantation in Patients with Advanced COVID-19: Two Case Reports.

BACKGROUND: Lung transplantation might be a viable alternative for patients with irreversible lung injury secondary to coronavirus disease 2019 (COVID-19). Here, we describe two patients with end-stage COVID-19 that received lung transplantations, the clinical-radiologic manifestations of postoperative complications, and the imaging features of allograft rejection. CASE PRESENTATION: In case 1, a 66-year-old woman presented severe hypoxia after lung transplantation. Chest imaging revealed diffuse homogeneous infiltration in the donor's lung. Dramatic resolution of the imaging abnormalities after intravenous administration of methylprednisolone favored a diagnosis of hyperacute rejection. The second is a 70-year-old man who was infected with bacterial postoperatively. During the empiric antibiotic therapy, chest CT showed newly developed groundglass opacities with septal thickening, suggesting a diagnosis of acute rejection. High-dose corticosteroids therapy was initiated, and the patient recovered gradually. CONCLUSION: This is the first report describing postoperative complications of lung transplantation in patients with advanced COVID-19. We presumed that imaging procedures could be a useful tool in early detecting lung transplant complications and selecting specific interventions for patients with COVID-19.

Sex-specific plasticity in CRF regulation of inhibitory control in central amygdala CRF1 neurons after chronic voluntary alcohol drinking.

Despite strong preclinical evidence for the ability of corticotropin releasing factor 1 (CRF1) antagonists to regulate alcohol consumption, clinical trials have not yet demonstrated therapeutic effects of these compounds in alcohol use disorder (AUD) patients. Several confounding factors may limit the translation of preclinical CRF1 research to patients, including reliance on experimenter-administered alcohol instead of voluntary consumption, a preponderance of evidence collected in male subjects only and an inability to assess the effects of alcohol on specific brain circuits. A population of particular interest is the CRF1-containing neurons of the central amygdala (CeA). CRF1 CeA neurons are sensitive to ethanol, but the effects of alcohol drinking on CRF signalling within this population are unknown. In the present study, we assessed the effects of voluntary alcohol drinking on inhibitory control of CRF1+ CeA neurons from male and female CRF1:GFP mice using ex vivo electrophysiology and determined the contributions of CRF1 signalling to inhibitory control and voluntary alcohol drinking. Chronic alcohol drinking produced neuroadaptations in CRF1+ neurons that increased the sensitivity of GABAA receptor-mediated sIPSCs to the acute effects of alcohol, CRF and the CRF1 antagonist R121919, but these adaptations were more pronounced in male versus female mice. The CRF1 antagonist CP-154,526 reduced voluntary alcohol drinking in both sexes and abolished sex differences in alcohol drinking. The lack of alcohol-induced adaptation in the female CRF1 system may be related to the elevated alcohol intake exhibited by female mice and could contribute to the ineffectiveness of CRF1 antagonists in female AUD patients.

Medial prefrontal cortex-basolateral amygdala circuit dysfunction in chronic alcohol-exposed male rats.

Alcohol is a commonly used drug that can produce alcohol use disorders (AUDs). Few individuals with AUDs receive treatment and treatment options are complicated by issues with effectiveness and compliance. Alcohol has been shown to differentially affect specific brain regions and an improved understanding of circuit-specific dysregulation caused by alcohol is warranted. Previous work has implicated both the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) in alcohol-associated plasticity, however studies directly examining the impact of alcohol exposure on this circuit are lacking. The current study employed an optogenetic strategy to investigate the prelimbic mPFC to BLA circuit and changes in circuit activity following chronic intragastric ethanol exposure in male Sprague Dawley rats. We observed monosynaptic connections with light-evoked stimulation of mPFC terminals in the BLA with efficacy and short latency. We also found that mPFC-BLA projections are primarily glutamatergic under basal inhibitory control, with a lesser population of GABAergic projections. We examined optically-evoked glutamate currents in the BLA using repeated trains of stimulation that displayed accommodation, or a reduction in evoked current amplitude over repeated stimulations. We found that following chronic ethanol exposure mPFC-BLA glutamatergic connections were dysregulated such that there were decreases in overall function, notably in synaptic strength and accommodation, with no change in probability of evoked glutamate release. The lesser GABAergic component of the mPFC-BLA circuit was not altered by chronic ethanol exposure. Collectively these data indicate that mPFC-BLA circuitry is a significant target of alcohol-associated plasticity, which may contribute to pathological behavior associated with AUDs.

Clinical use of platelet-rich fibrin in the repair of non-healing incision wounds after fibular fracture surgery: A case report.

RATIONALE: This report describes rehabilitation for a 53-year-old female recovering from non-healing skin and soft tissue defect after distal tibial open fracture by using platelet-rich fibrin topical repair following an automobile accident. PATIENT CONCERNS: The patient was admitted to a rehabilitation specialty hospital approximately 1 year post a fracture of the distal left tibiofibula and separate surgical tibiofibular fracture incision and internal fixation + bone grafting. DIAGNOSES: Clinical presentation included the left ankle incision was interrupted for about 3 cm with poor healing, a small amount of muscle necrosis, fat liquefaction, a large amount of yellow purulent secretion overflow and necrotic material was seen in the local wound. INTERVENTIONS: Platelet rich fibrin (PRF) gel was injected into the wounds and submerged sites to make full contact with the wounds and close the wounds with the autologous platelet-rich fibrin prepared by mixing, and then covered with oil gauze to keep the wounds moist and promote granulation growth. The outermost layer was covered with cotton pads. OUTCOMES: After 30 days of 2 PRF treatments, the skin defect was healed and no significant abnormality was observed at 6 months follow-up. LESSONS: Treatment with topical autologous platelet-rich plasma gel Significantly accelerates the healing of wounds, shortens healing time, improves healing quality and reduces scar formation without significant adverse effects.

A comparison of the effects of fire needle and routine acupuncture for myofascitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Myofascitis is a common disease in clinic. The main cause of the disease is aseptic inflammation of local muscles and connective tissues such as myofascial, which can be manifested as paralysis, distension, and other discomfort, local muscle stiffness, spasm or palpable strain-like nodules. Chinese medicine ascribes it to "bi disease" and "Arthralgia disease," while Western medicine believes that the disease is mainly due to local muscle and fascia edema and exudation caused by trauma or long-term strain, forcing nerves to jam and producing pain and other abnormal feelings. Although the disease is not life-threatening, the pain and distension caused by local inflammatory stimuli can affect the patient's daily life and sleep quality. The purpose of this systematic review is to evaluate the efficacy of fire needle vs routine acupuncture in the treatment of myofascitis. METHODS: Randomized controlled trials (RCTS) of fire needle vs routine acupuncture for myofascial inflammation will be comprehensively searched from inception to September 2020 on PubMed, Embase, Cochrane Library, China Biomedical Literature (CBM), China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), and Wanfang. Additionally, RCT registered sites, including http://www.ClinicalTrials.gov and http://www.chictr.org.cn, also will be the search. Visual analogue scale (VAS) was used to score the pain before and after treatment. The primary outcome will be to compare the difference in pain scores between the 2 interventions. Two independent authors filtered the literature in the above database, extracted the data, and cross-checked it. RESULTS: This study will offer a reasonable comprehensive evidence for the treatment of myofascitis with fire needle. CONCLUSION: The conclusion of this study will provide evidence to judge the effectiveness of fire needle on myofascitis. REGISTRATION NUMBER: INPLASY202080034.

Effect of quadratus lumborum block on postoperative cognitive function in elderly patients undergoing laparoscopic radical gastrectomy: a randomized controlled trial.

BACKGROUND: Quadratus lumborum block (QLB) is a novel and effective postoperative analgesia method for abdominal surgeries. However, whether QLB can affect early postoperative cognitive function by inhibiting surgical traumatic stress and the inflammatory response remains unclear. This study aimed to explore the effect of QLB on postoperative cognitive function in elderly patients undergoing laparoscopic radical gastrectomy. METHODS: Sixty-four elderly patients who underwent laparoscopic radical gastrectomy were randomly divided into the QLB group (Q group, n = 32) and control group (C group, n = 32). The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to measure cognitive function 1 day before and 7 days after surgery. Postoperative cognitive dysfunction (POCD) was defined as a decline of ≥ 1 SD in both tests. The visual analog scale (VAS) scores 6 h (T1), 24 h (T2), and 48 h (T3) after surgery were measured. The serum levels of high mobility group box protein 1 (HMGB1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated 1 day before surgery (baseline), and 1 day (day 1) and 3 days after surgery (day 3). The intraoperative remifentanil dosage, sufentanil consumption 24 h after surgery, recovery time from anesthesia, and adverse effects were also compared. RESULTS: POCD was present in two patients in the QLB group and eight patients in the C group 7 days after surgery (6.7 % vs. 27.6 %, P = 0.032). The MMSE and MoCA scores were similar in both groups preoperatively, and the two scores were higher in the QLB group than in the C group 7 days after surgery (P < 0.05). The VAS scores were significantly lower in the Q group at all times after surgery (P < 0.05). Compared with the C group, the levels of HMGB1, TNF-α, and IL-6 were significantly decreased 1 and 3 days after surgery in the QLB group (P < 0.05). The remifentanil consumption intraoperatively and sufentanil 24 h postoperatively were significantly lower in the QLB group (P < 0.05). The recovery time from anesthesia was shorter in the QLB group (P < 0.05). No severe adverse effects occurred in either group. CONCLUSIONS: QLB could improve postoperative cognitive function in elderly patients undergoing laparoscopic radical gastrectomy. This may be related to the suppression of the inflammatory response after surgery. TRIAL REGISTRATION: Chictr.org.cn identifier ChiCTR1900027574 (Date of registry: 19/11/2019, prospectively registered).

Acupuncture for drooling in children with cerebral palsy: A protocol for systematic review.

BACKGROUND: The aim of this study is to provide the methods used to evaluate the effectiveness and safety of acupuncture therapy for treating drooling in children with cerebral palsy. METHODS AND ANALYSIS: A comprehensive search of Pubmed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, 4 Chinese databases (China National Knowledge Infrastructure, Chinese Biomedical Literatures database, Wan-Fang Database and Chinese Science and Technology Periodicals will be conducted to identify randomized controlled trials of acupuncture for treating children with cerebral palsy salivation with no restriction on time or language. The primary outcome of this systematic review will be the effective rate. The risk of bias will be implemented according to Cochrane Handbook for Systematic Reviews of Interventions. We will conduct the meta-analysis to synthesize the evidence for each outcome, if possible. The heterogeneity will be evaluated statistically using the χ2 test and the I2 statistic. The random-effect model will be used to provide more conservative results, if significant heterogeneity is identified (I2 > 50% or P < .10). ETHICS/DISSEMINATION: Our findings will be disseminated in a peer-reviewed journal and at conference meetings. It is not necessary for formal ethical approval as no primary data are collected. TRIAL REGISTRATION NUMBER: INPLASY2020110024.

Different acupuncture therapies combined with rehabilitation in the treatment of scapulohumeral periarthritis: A protocol for systematic review and network meta-analysis.

BACKGROUND: Scapulohumeral periarthritis is a disease that seriously affects human daily work and life, and greatly reduces peoples quality of life and affects human health all over the world. Now, many studies have shown that acupuncture and rehabilitation have a significant effect on scapulohumeral periarthritis. In this study, network meta-analysis was used to analyze and compare the clinical efficacy and difference of different acupuncture treatments on scapulohumeral periarthritis. METHODS: All patients were diagnosed as scapulohumeral periarthritis by randomized controlled trial. Computer searches will be conducted on CNKI, Wan-Fang databases, VIP, CBM, Pubmed, Cochrane library, Embase, Web of Science. The retrieval period is from the date of database establishment to September 8, 2020. To avoid omissions, we will manually retrieve relevant references and conference papers. Finally, the risk of bias included in the study will be assessed according to the guidelines of the Cochrane Handbook for systematic review of interventions. All data analysis will be performed by Revman 5.3, WinBUGS1.4.3 and Stata14.2. RESULTS: The effectiveness of each intervention was quantified. The main results included cure rate, total effective rate, VAS score and shoulder function score. CONCLUSION: Objective to provide evidence-based medicine basis for clinicians to choose more effective acupuncture therapy for scapulohumeral periarthritis. INPLASY REGISTRATION NUMBER: 202090035.

Functional Dissection of Basal Ganglia Inhibitory Inputs onto Substantia Nigra Dopaminergic Neurons.

Substantia nigra (SNc) dopaminergic neurons respond to aversive stimuli with inhibitory pauses in firing followed by transient rebound activation. We tested integration of inhibitory synaptic inputs onto SNc neurons from genetically defined populations in dorsal striatum (striosome and matrix) and external globus pallidus (GPe; parvalbumin- and Lhx6-positive), and examined their contribution to pause-rebound firing. Activation of striosome projections, which target "dendron bouquets" in the pars reticulata (SNr), consistently quiets firing and relief from striosome inhibition triggers rebound activity. Striosomal inhibitory postsynaptic currents (IPSCs) display a prominent GABA-B receptor-mediated component that strengthens the impact of SNr dendrite synapses on somatic excitability and enables rebounding. By contrast, GPe projections activate GABA-A receptors on the soma and proximal dendrites but do not result in rebounding. Lastly, optical mapping shows that dorsal striatum selectively inhibits the ventral population of SNc neurons, which are intrinsically capable of rebounding. Therefore, we define a distinct striatonigral circuit for generating dopamine rebound.

Corticotropin-Releasing Factor Receptor-1 Neurons in the Lateral Amygdala Display Selective Sensitivity to Acute and Chronic Ethanol Exposure.

The lateral amygdala (LA) serves as the point of entry for sensory information within the amygdala complex, a structure that plays a critical role in emotional processes and has been implicated in alcohol use disorders. Within the amygdala, the corticotropin-releasing factor (CRF) system has been shown to mediate some of the effects of both stress and ethanol, but the effects of ethanol on specific CRF1 receptor circuits in the amygdala have not been fully established. We used male CRF1:GFP reporter mice to characterize CRF1-expressing (CRF1+) and nonexpressing (CRF1-) LA neurons and investigate the effects of acute and chronic ethanol exposure on these populations. The CRF1+ population was found to be composed predominantly of glutamatergic projection neurons with a minority subpopulation of interneurons. CRF1+ neurons exhibited a tonic conductance that was insensitive to acute ethanol. CRF1- neurons did not display a basal tonic conductance, but the application of acute ethanol induced a δ GABAA receptor subunit-dependent tonic conductance and enhanced phasic GABA release onto these cells. Chronic ethanol increased CRF1+ neuronal excitability but did not significantly alter phasic or tonic GABA signaling in either CRF1+ or CRF1- cells. Chronic ethanol and withdrawal also did not alter basal extracellular GABA or glutamate transmitter levels in the LA/BLA and did not alter the sensitivity of GABA or glutamate to acute ethanol-induced increases in transmitter release. Together, these results provide the first characterization of the CRF1+ population of LA neurons and suggest mechanisms for differential acute ethanol sensitivity within this region.

Cannabidiol attenuates seizures and EEG abnormalities in Angelman syndrome model mice.

Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, lack of speech, ataxia, EEG abnormalities, and epilepsy. Seizures in individuals with AS are common, debilitating, and often drug resistant. Thus, there is an unmet need for better treatment options. Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, has shown antiseizure activity and behavioral benefits in preclinical and clinical studies for some disorders associated with epilepsy, suggesting that the same could be true for AS. Here, we show that acute CBD (100 mg/kg) treatment attenuated hyperthermia- and acoustically induced seizures in a mouse model of AS. However, neither acute CBD nor a 2-week-long course of CBD administered immediately after a kindling protocol could halt the proepileptogenic plasticity observed in AS model mice. CBD had a dose-dependent sedative effect but did not have an impact on motor performance. CBD abrogated the enhanced intracortical local field potential power, including the delta and theta rhythms observed in AS model mice, indicating that CBD administration could also help normalize the EEG deficits observed in individuals with AS. We believe our results provide critical preclinical evidence supporting CBD treatment of seizures and alleviation of EEG abnormalities in AS and will thus help guide the rational development of CBD as a treatment for AS.