Cannabidiol (CBD), a non-psychoactive cannabinoid, shows great promise in treating methamphetamine (METH) addiction. Nonetheless, the molecular target and the mechanism through which CBD treats METH addiction remain unexplored. Herein, CBD was shown to counteract METH-induced locomotor sensitization and conditioned place preference. Additionally, CBD mitigated the adverse effects of METH, such as cristae loss, a decline in ATP content, and a reduction in membrane potential. Employing an activity-based protein profiling approach, a target fishing strategy was used to uncover CBD's direct target. ATP5A1, a subunit of ATP synthase, was identified and validated as a CBD target. Moreover, CBD demonstrated the ability to ameliorate METH-induced ubiquitination of ATP5A1 via the D376 residue, thereby reversing the METH-induced reduction of ATP5A1 and promoting the assembly of ATP synthase. Pharmacological inhibition of the ATP efflux channel pannexin 1, blockade of ATP hydrolysis by a CD39 inhibitor, and blocking the adenosine A1 receptor (A1R) all attenuated the therapeutic benefits of CBD in mitigating METH-induced behavioral sensitization and CPP. Moreover, the RNA interference of ATP5A1 in the ventral tegmental area resulted in the reversal of CBD's therapeutic efficacy against METH addiction. Collectively, these data show that ATP5A1 is a target for CBD to inhibit METH-induced addiction behaviors through the ADO-A1R signaling pathway.

Predatory hunting is an important type of innate behavior evolutionarily conserved across the animal kingdom. It is typically composed of a set of sequential actions, including prey search, pursuit, attack, and consumption. This behavior is subject to control by the nervous system. Early studies used toads as a model to probe the neuroethology of hunting, which led to the proposal of a sensory-triggered release mechanism for hunting actions. More recent studies have used genetically-trackable zebrafish and rodents and have made breakthrough discoveries in the neuroethology and neurocircuits underlying this behavior. Here, we review the sophisticated neurocircuitry involved in hunting and summarize the detailed mechanism for the circuitry to encode various aspects of hunting neuroethology, including sensory processing, sensorimotor transformation, motivation, and sequential encoding of hunting actions. We also discuss the overlapping brain circuits for hunting and feeding and point out the limitations of current studies. We propose that hunting is an ideal behavioral paradigm in which to study the neuroethology of motivated behaviors, which may shed new light on epidemic disorders, including binge-eating, obesity, and obsessive-compulsive disorders.
Animals ; Zebrafish ; Hunting ; Predatory Behavior/physiology* ; Neurons/physiology* ; Motivation

Objective:To compare the Application of the trapezius squeeze and jaw thrust in laryngeal mask airway (LMA) in-sertion in children under sevoflurane anesthesia .Methods:A total of 80 children aged 4 to 10 ,American Society of Anesthesiol-ogists(ASA) I-II and undergoing minor operation such as indirect hernia repair and orchiopexy were enrolled and randomly de-vived into trapezius squeezing group(Group T ,n= 40) and jaw thrusting group (Group J ,n= 40) .Anesthisia was induced with 6 L/min oxygen and 8% sevoflurane .When the chileren’s eyelash reflex lose ,jaw thrust/trapezius squeeze was applied every 10 s .The LMA was inserted immediately after the response of childern to trapezius squeeze or jaw thrust disppeared .The successful rates of LMA insertion ,LAM insertion time ,and blood pressure(BP) and heart rate(HR) before and after LMA in-sertion ,end-tidal sevoflurane concentrations (ETsev) ,minimum alveolar concentrations (MAC) in two groups were Recorded and compared .Results:The successful rate of the LMA insertion in Group T (95% ,38/40) was significantly higher than that in the Group J (75% ,30/40) ,there was statistical difference(P= 0 .013);The LMA insertion time in Group T was longer than that in Group J (P=0 .000);the untoward effects in Group T were less than those in Group J ;The BP ,HR ,ETsev ,MAC in two groups had not statistical differences .Conclusions :The trapezius squeeze is more sutable than jaw thrust for assessment of anaesthetic depth in LM A insertion in chilren under sevoflurane anesthesia .

Objective To determine the serum levels of B cell activating factor-receptor(BAFF-R)in patients with primary Sj(o)gren's syndrome(pSS)and investigate the role of BAFF-R in the pathogenesis of pSS.Methods The serum concentration of BAFF-R was measured by ELISA in 120 patients with pSS and 62 age-and sex-matched normal controls.Results The median level of serum BAFF-R was(692.7 ± 536.9)ng/L in pSS and (279.7 ± 186.9)ng/L in healthy controls.The serum level of BAFF-R in the pSS was significantly higher than normal controls(P ＜0.01).Higher level of BAFF-R was associated with higher level of IgG(r =0.429,P ＜0.01).Serum level of BAFF-R had no correlation with IgA,IgM,C3,C4,RF,ESR and CRP.BAFF-R level was markedly increased in patients with positive ANA,anti-SSA,anti-SSB antibody compared with those with negative antibody.Conclusion The serum BAFF-R level was significantly elevated and correlated with the level of immunoglobulin and autoantibodies.BAFF-R play certain role in the pathogenesis of pSS.

Objective To assess the efficacy and safety of diclofenac sodium paste in the treatment of primary osteoarthritis(OA).Methods 54 patients with primary OA were divided into two groups.The experiment group received diclofenac sodium paste.The control group received diclofenac sodium(votalin) emulgel.Patient global assessment and topical pain assessment,physician global assessment and topical pain assessment were wrote down at baseline and after final application.Safety was assessed by evaluation of adverse events,vital signs,and irritation at the application site.Results There were no significant difference between experiment group and control group in patient global assessment,patient pain assessment,physician global assessment,and physician pain assessment.No serious gastrointestinal or renal adverse events were reported or detected by means of laboratory testing.Conclusion Diclofenac sodium paste is effective and safe in the treatment of primary OA.

Objective To investigate clinical and pathological features of autoimmune cholangitis (AIC) in antimitochondrial antibody (AMA) positive and negative patients.Method According to AMA presence or absence,37 primary biliary cirrhosis (PBC) patients were assigned to AMA positive group and AIC group.Clinical and pathological differences between two groups were compared.Results No differences were found in the level of liver function,liver cirrhosis,frequency of cholestasis and bile duct lesions between two groups.However,lower serum level of alkaline phosphatase,severer hepatocellular damage in pathology and higher AIH score were found in AIC group.Therefore the frequency accompanied by Sjgren′s syndrome (SS) in AIC group was significant higher.Conclusion AIC group is companied by slighter cholestasis and severer damage of hepatocytes indicating more autoimmune findings of AIC patients.AIC may have some correlation with SS in etiology and pathogenesis.