Growth phase-dependent reorganization of cryptophyte photosystem I antennae.

Photosynthetic cryptophytes are eukaryotic algae that utilize membrane-embedded chlorophyll a/c binding proteins (CACs) and lumen-localized phycobiliproteins (PBPs) as their light-harvesting antennae. Cryptophytes go through logarithmic and stationary growth phases, and may adjust their light-harvesting capability according to their particular growth state. How cryptophytes change the type/arrangement of the photosynthetic antenna proteins to regulate their light-harvesting remains unknown. Here we solve four structures of cryptophyte photosystem I (PSI) bound with CACs that show the rearrangement of CACs at different growth phases. We identify a cryptophyte-unique protein, PsaQ, which harbors two chlorophyll molecules. PsaQ specifically binds to the lumenal region of PSI during logarithmic growth phase and may assist the association of PBPs with photosystems and energy transfer from PBPs to photosystems.

The effect of adding real-time postural feedback in balance and mobility training in older adults: A systematic review and meta-analysis.

OBJECTIVES: This study aimed to systematically review the additional value of providing real-time postural feedback during balance and mobility training in older people. METHODS: PubMed, Embase, CINAHL, and Web-of-Science were searched from inception to August 2023. Studies comparing the effectiveness of feedback-based versus non-feedback-based postural balance or mobility training on balance or mobility outcomes were selected. Similar outcomes were pooled in meta-analyses using a random-effect model. The quality of evidence for available outcomes was rated by Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Eight studies were identified with 203 subjects. Two studies showed that providing postural feedback immediately improved stability in static balance and gait. For the post-training effect, however, no significant change was found in trunk movement during single-leg standing (i.e., pitch angle, MD=0.65, 95 %CI=-0.77 to 2.07, low-quality; roll angle, MD=0.96, 95 %CI=-0.87 to 2.80, moderate-quality), in the Mini-BESTest (MD=1.88, 95 %CI=-0.05 to 3.80, moderate-quality), and in balance confidence (MD=0.29, 95 %CI=-3.43 to 4.2, moderate-quality). A worsened functional reach distance was associated with providing feedback during balance training (MD=-3.26, 95 %CI=-6.31 to -0.21, high-quality). Meta-analyses on mobility outcomes were mostly insignificant, except for the trunk-roll angle of walking (MD=0.87, 95 %CI=0.05 to 1.70, low-quality) and trunk-pitch angle of walking with head-turning (MD=1.87, 95 %CI=0.95 to 2.79, moderate-quality). CONCLUSION: Adding real-time postural feedback to balance and mobility training might immediately improve stability in balance and mobility in older people. However, mixed results were reported for its post-training effect.

Regulatory mechanism of the six-method massage antipyretic process on lipopolysaccharide-induced fever in juvenile rabbits: A targeted metabolomics approach.

Objective: To investigate the mechanism of the six-method massage antipyretic process (SMAP) and its influence on the body's metabolic state. Methods: The random number table method was used to divide 24 New Zealand 2-month-old rabbits with qualified basal body temperature into a control group, model group and massage group (n = 8 per group). The model group and massage groups were injected with 0.5 µg/ml lipopolysaccharide (1 ml/kg) into the auricular vein, and the control group was injected with the same amount of normal saline at the same temperature. One hour after modelling, the massage group was given SMAP (opening Tianmen, pushing Kangong, rubbing Taiyang, rubbing Erhougaogu, clearing the Tianheshui and pushing the spine). The change of anal temperature 5 h after moulding was recorded to clarify the antipyretic effect. Results: After modelling, the rectal temperature of the juvenile rabbits in the three groups increased. The rectal temperature of the model group was higher than that of the control group 5 h after modelling, and the rectal temperature of the massage group was lower than that of the model group (P < 0.05). The antipyretic mechanism is related to the regulation of the synthesis of phenylalanine, tyrosine and tryptophan, as well as the pentose phosphate pathway. Compared with the model group, the plasma interleukin (IL)-1, IL-6, interferon-gamma, toll-like receptor 4, nuclear factor κB, the mechanistic target of rapamycin complex 1, indoleamine 2,3-dioxygenase 1, aryl hydrocarbon receptor, liver aspartate transaminase (AST), alanine transaminase (ALT) and l-glutamate dehydrogenase (L-GLDH) expression in the massage group were significantly decreased (P < 0.05). Compared with the model group, the massage group had significantly reduced AST, ALT and L-GLDH expression in plasma (P < 0.05). Conclusion: The mechanism of SMAP therapy is related to regulating the expression of peripheral inflammatory factors and metabolic pathways.

Research Progress on the Pathogenesis of Knee Osteoarthritis.

Knee osteoarthritis (KOA) is a chronic joint bone disease characterized by inflammatory destruction and hyperplasia of bone. Its main clinical symptoms are joint mobility difficulties and pain, severe cases can lead to limb paralysis, which poses major pressure to the quality of life and mental health of patients, but also brings serious economic burden to society. The occurrence and development of KOA is influenced by many factors, including systemic factors and local factors. The joint biomechanical changes caused by aging, trauma and obesity, abnormal bone metabolism caused by metabolic syndrome, the effects of cytokines and related enzymes, genetic and biochemical abnormalities caused by plasma adiponectin, etc. all directly or indirectly lead to the occurrence of KOA. However, there is little literature that systematically and comprehensively integrates macro- and microscopic KOA pathogenesis. Therefore, it is necessary to comprehensively and systematically summarize the pathogenesis of KOA in order to provide a better theoretical basis for clinical treatment.

Association of Intraoperative Opioid Administration With Postoperative Pain and Opioid Use.

Importance: Opioids administered to treat postsurgical pain are a major contributor to the opioid crisis, leading to chronic use in a considerable proportion of patients. Initiatives promoting opioid-free or opioid-sparing modalities of perioperative pain management have led to reduced opioid administration in the operating room, but this reduction could have unforeseen detrimental effects in terms of postoperative pain outcomes, as the relationship between intraoperative opioid usage and later opioid requirements is not well understood. Objective: To characterize the association between intraoperative opioid usage and postoperative pain and opioid requirements. Design, Setting, and Participants: This retrospective cohort study evaluated electronic health record data from a quaternary care academic medical center (Massachusetts General Hospital) for adult patients who underwent noncardiac surgery with general anesthesia from April 2016 to March 2020. Patients who underwent cesarean surgery, received regional anesthesia, received opioids other than fentanyl or hydromorphone, were admitted to the intensive care unit, or who died intraoperatively were excluded. Statistical models were fitted on the propensity weighted data set to characterize the effect of intraoperative opioid exposures on primary and secondary outcomes. Data were analyzed from December 2021 to October 2022. Exposures: Intraoperative fentanyl and intraoperative hydromorphone average effect site concentration estimated using pharmacokinetic/pharmacodynamic models. Main Outcomes and Measures: The primary study outcomes were the maximal pain score during the postanesthesia care unit (PACU) stay and the cumulative opioid dose, quantified in morphine milligram equivalents (MME), administered during the PACU stay. Medium- and long-term outcomes associated with pain and opioid dependence were also evaluated. Results: The study cohort included a total of 61 249 individuals undergoing surgery (mean [SD] age, 55.44 [17.08] years; 32 778 [53.5%] female). Increased intraoperative fentanyl and intraoperative hydromorphone were both associated with reduced maximum pain scores in the PACU. Both exposures were also associated with a reduced probability and reduced total dosage of opioid administration in the PACU. In particular, increased fentanyl administration was associated with lower frequency of uncontrolled pain; a decrease in new chronic pain diagnoses reported at 3 months; fewer opioid prescriptions at 30, 90, and 180 days; and decreased new persistent opioid use, without significant increases in adverse effects. Conclusions and Relevance: Contrary to prevailing trends, reduced opioid administration during surgery may have the unintended outcome of increasing postoperative pain and opioid consumption. Conversely, improvements in long-term outcomes might be achieved by optimizing opioid administration during surgery.

Individualized Electrode Subset Improves the Calibration Accuracy of an EEG P300-design Brain-Computer Interface for People with Severe Cerebral Palsy.

Objective: This study examined the effect of individualized electroencephalogram (EEG) electrode location selection for non-invasive P300-design brain-computer interfaces (BCIs) in people with varying severity of cerebral palsy (CP). Approach: A forward selection algorithm was used to select the best performing 8 electrodes (of an available 32) to construct an individualized electrode subset for each participant. BCI accuracy of the individualized subset was compared to accuracy of a widely used default subset. Main Results: Electrode selection significantly improved BCI calibration accuracy for the group with severe CP. Significant group effect was not found for the group of typically developing controls and the group with mild CP. However, several individuals with mild CP showed improved performance. Using the individualized electrode subsets, there was no significant difference in accuracy between calibration and evaluation data in the mild CP group, but there was a reduction in accuracy from calibration to evaluation in controls. Significance: The findings suggested that electrode selection can accommodate developmental neurological impairments in people with severe CP, while the default electrode locations are sufficient for many people with milder impairments from CP and typically developing individuals.

Marginal donor liver versus standard donor liver: A single-center observational study.

BACKGROUND: The effectiveness and safety of marginal donor livers remain controversial. This study aimed to investigate the clinical efficacy of marginal donor livers in patients with liver transplantation (LT). METHODS: This study included 199 liver donors (including 16 split donors) and 206 liver recipients from January 1, 2018 to January 27, 2020, with case follow-up until July 31, 2021. Clinical data of donors and recipients were retrospectively analyzed and were divided into the marginal donor and standard donor groups according to the criteria of marginal donor livers. Indices of liver and kidney functions, complications, and survival curves of the two groups were compared. RESULTS: Compared with the standard donor group, the blood creatinine levels were significantly higher in the marginal donor group in the first week after operation (P < 0.05); there were no significant differences in alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels after LT (all P > 0.05); there was no significant difference in the incidence of complications after LT (P > 0.05); there was also no significant difference in the survival curve (P = 0.335). CONCLUSIONS: There were no significant differences in liver and kidney function and survival curve between the standard donor and marginal donor groups. The marginal donor liver appears safe and reliable for LT and may be an important strategy to expand the donor pool and solve the shortage of organs.

Effects of cadmium chloride on testicular autophagy and blood-testis barrier integrity in prepubertal male rats / 中华劳动卫生职业病杂志

Objective: To study the effects of cadmium chloride (CdCl(2)) exposure on testicular autophagy levels and blood-testis barrier integrity in prepubertal male SD rats and testicular sertoli (TM4) cells. Methods: In July 2021, 9 4-week-old male SD rats were randomly divided into 3 groups: control group (normal saline), low dose group (1 mg/kg·bw CdCl(2)) and high dose group (2 mg/kg·bw CdCl(2)), and were exposed with CdCl(2) by intrabitoneal injection. 24 h later, HE staining was used to observe the morphological changes of testis of rats, biological tracer was used to observe the integrity of blood-testis barrier, and the expression levels of microtubule-associated protein light chain 3 (LC3) -Ⅰ and LC3-Ⅱ in testicular tissue were detected. TM4 cells were treated with 0, 2.5, 5.0 and 10.0 μmol/L CdCl(2) for 24 h to detect the toxic effect of cadmium. The cells were divided into blank group (no exposure), exposure group (10.0 μmol/L CdCl(2)), experimental group[10.0 μmol/L CdCl(2)+60.0 μmol/L 3-methyladenine (3-MA) ] and inhibitor group (60.0 μmol/L 3-MA). After 24 h of treatment, Western blot analysis was used to detect the expression levels of LC3-Ⅱ, ubiquitin binding protein p62, tight junction protein ZO-1 and adhesion junction protein N-cadherin. Results: The morphology and structure of testicular tissue in the high dose group were obvious changed, including uneven distribution of seminiferous tubules, irregular shape, thinning of seminiferous epithelium, loose structure, disordered arrangement of cells, abnormal deep staining of nuclei and vacuoles of Sertoli cells. The results of biological tracer method showed that the integrity of blood-testis barrier was damaged in the low and high dose group. Western blot results showed that compared with control group, the expression levels of LC3-Ⅱ in testicular tissue of rats in low and high dose groups were increased, the differences were statistically significant (P<0.05). Compared with the 0 μmol/L, after exposure to 5.0, 10.0 μmol/L CdCl(2), the expression levels of ZO-1 and N-cadherin in TM4 cells were significantly decreased, and the expression level of p62 and LC3-Ⅱ/LC3-Ⅰ were significantly increased, the differences were statistically significant (P<0.05). Compared with the exposure group, the relative expression level of p62 and LC3-Ⅱ/LC3-Ⅰ in TM4 cells of the experimental group were significantly decreased, while the relative expression levels of ZO-1 and N-cadherin were significantly increased, the differences were statistically significant (P<0.05) . Conclusion: The mechanism of the toxic effect of cadmium on the reproductive system of male SD rats may be related to the effect of the autophagy level of testicular tissue and the destruction of the blood-testis barrier integrity.

SNTA1-deficient human cardiomyocytes demonstrate hypertrophic phenotype and calcium handling disorder.

BACKGROUND: α-1-syntrophin (SNTA1), a protein encoded by SNTA1, is highly expressed in human cardiomyocytes. Mutations in SNTA1 are associated with arrhythmia and cardiomyopathy. Previous research on SNTA1 has been based on non-human cardiomyocytes. This study was designed to identify the phenotype of SNTA1-deficiency using human cardiomyocytes. METHODS: SNTA1 was knocked out in the H9 embryonic stem cell line using the CRISPR-Cas9 system. H9SNTA1KO cells were then induced to differentiate into cardiomyocytes using small molecule inhibitors. The phenotypic discrepancies associated with SNTA1-deficient cardiomyocytes were investigated. RESULTS: SNTA1 was truncated at the 149th amino acid position of PH1 domain by a stop codon (TGA) using the CRISPR-Cas9 system. SNTA1-deficiency did not affect the pluripotency of H9SNTA1KO, and they retain their in vitro ability to differentiate into cardiomyocytes. However, H9SNTA1KO derived cardiomyocytes exhibited hypertrophic phenotype, lower cardiac contractility, weak calcium transient intensity, and lower level of calcium in the sarcoplasmic reticulum. Early treatment of SNTA1-deficient cardiomyocytes with ranolazine improved the calcium transient intensity and cardiac contractility. CONCLUSION: SNTA1-deficient cardiomyocytes can be used to research the etiology, pathogenesis, and potential therapies for myocardial diseases. The SNTA1-deficient cardiomyocyte model suggests that the maintenance of cardiac calcium homeostasis is a key target in the treatment of myocardial-related diseases.

A circuit from dorsal hippocampal CA3 to parvafox nucleus mediates chronic social defeat stress-induced deficits in preference for social novelty.

The preference for social novelty is crucial to the social life of humans and rodents. However, the neural mechanisms underlying social novelty preference are poorly understood. Here, we found that chronic social defeat stress (CSDS) reduced the preference for social novelty in mice by impairing the response of CaMKIIα+ neurons in the CA3 region of dorsal hippocampus (dCA3) during approach to an unfamiliar mouse. The deficits of social novelty preference in CSDS-treated mice were reversed by activating the output from dCA3 to the GABAergic neurons in the lateral septum (LS). The activation of GABAergic projection from LS recruited a circuit that inhibited the Foxb1+ neurons in the parvafox nucleus (PFN), which drove social avoidance by projecting to the lateral periaqueductal gray (lPAG). These results suggest that a previously unidentified circuit of dCA3CaMKIIα+→LSGABA+→PFNFoxb1+→lPAG mediates the deficits of social novelty preference induced by CSDS.

Determining structures in a native environment using single-particle cryoelectron microscopy images.

Cryo-electron tomography is a powerful tool for structure determination in the native environment. However, this method requires the acquisition of tilt series, which is time-consuming and severely slows structure determination. By treating the densities of non-target protein as non-Gaussian noise, we developed a new target function that greatly improves the efficiency of recognizing the target protein in a single cryo-electron microscopy image. Moreover, we developed a sorting function that effectively eliminates the model dependence and improved the resolution during the subsequent structure refinement procedure. By eliminating model bias, our method allows using homolog proteins as models to recognize the target proteins in a complex context. Together, we developed an in situ single-particle analysis method. Our method was successfully applied to solve structures of glycoproteins on the surface of a non-icosahedral virus and Rubisco inside the carboxysome. Both data were collected within 24 h, thus allowing fast and simple structural determination.

Morphological consequences of upstream water and sediment changes and estuarine engineering activities in Pearl River Estuary channels over the last 50 years.

The relative contributions of decreased upstream sediment loads and local estuarine engineering activities to the estuarine channel geometry are poorly understood. In this study, we analyze the hydrological changes and identify the location, duration and intensity of the estuarine engineering activities based on the channel morphologic changes from 1965 to 2017 at the five stations in the Pearl River Estuary. Thereafter, the Mann-Kendall (M-K) statistical test, empirical orthogonal function (EOF) tests, and channel geometry reconstruction based on the hydrological coefficient were performed to quantitatively estimate the relative contributions from upstream dam construction and estuarine engineering activities. The results show that the geometric changes in the five transects over the last 50 years could be divided into three stages. Stage I extends over approximately 23-33 years at the different channel transects, during which the channel geometries were mainly influenced by natural factors, with a balance between erosion and deposition. Stage II occurred during the next 11-20 years and the changes in the cumulated water depth in comparison to the values in the previous adjacent years at this stage are approximately 5-25 times the values in stage I. The human activities (e.g., sand excavation) contribute to >70-90% of the extreme geometric changes. Stage III lasted for <3-11 years in the different transects with a slight depositional trend, and policies regulating sand excavation were implemented during this stage. The rapid increase in the channel area and water depth caused by sand excavation can cause the downcutting of the riverbed, a decrease in the water level, and redistribution of the water and sediment discharge. Therefore, the monitoring, simulation and analysis of the variation in the typical channel geometry over the long term provide important means to understand the human activities occurring and insights for future sustainable estuarine management.

The effects of Kctd12, an auxiliary subunit of GABAB receptor in dentate gyrus on behavioral response to chronic social defeat stress in mice.

Adaptive responses to stress are critical to enhance physical and mental well-being, but excessive or prolonged stress may cause inadaptability and increase the risks of psychiatric disorders, such as depression. GABABR signaling is fundamental to brain function and has been identified in neuropsychiatric disorders. KCTD12 is a critical auxiliary subunit in GABABR signaling, but its role in mental disorders, such as depression is unclear. In the present study, we used a well-validated mice model, chronic social defeat stress (CSDS) to investigate behavioral responses to stress and explore the role of Kctd12 in stress response, as well as the relevant mechanisms. We found that CSDS increased the expression of Kctd12 in the dentate gyrus (DG), a subregion of hippocampus. Overexpression of Kctd12 in DG induced higher responsiveness to acute stress and increased vulnerability to social stress in mice, whereas knock-down of Kctd12 in DG prevented the social avoidance. Furthermore, an increased expression of GABAB receptor 2 (GB2) in the DG of CSDS-treated mice was observed, and CGP35348, an antagonist of GABABR, improved the stress-induced behavior responses along with suppressing the excess expression of Kctd12. In addition, Kctd12 regulated the excitability of granule cell in DG, and the stimulation of neuronal activity by silencing Kctd12 contributed to the antidepressant-like effect of fluoxetine. These findings identify that the Kctd12 in DG works as a critical mediator of stress responses, providing a promising therapeutic target in stress-related psychiatric disorders, including depression.

Microglia: A Central Player in Depression.

Microglia are the major immune cells in the central nervous system and play a key role in the normal function of the brain. Microglia exhibit functional diversity, and they control the inflammation in central nervous system through releasing inflammatory cytokine, clearing apoptotic cells via phagocytosis, regulating synaptic plasticity and the formation of neural network by synapse pruning. Recent studies have strongly indicated that the microglial dysfunction is associated with a variety of neuropsychiatric diseases such as depression, which have been termed as "microgliopathy". The emergency of advanced technologies and tools has enabled us to comprehensively understand the role of microglia in physiology and pathology, and growing studies have targetted microglia to explore the treatment of neuropsychiatric diseases. Here, we describe the key progress of microglia research, and review the recent developments in the understanding of the role of microglia in physiology and etiology of depression.

Angiotensin-Converting Enzyme Inhibitor Rapidly Ameliorates Depressive-Type Behaviors via Bradykinin-Dependent Activation of Mammalian Target of Rapamycin Complex 1.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) are widely prescribed antihypertensive agents. Intriguingly, case reports and clinical trials have indicated that ACEIs, including captopril and lisinopril, may have a rapid mood-elevating effect in certain patients, but few experimental studies have investigated their value as fast-onset antidepressants. METHODS: The present study consisted of a series of experiments using biochemical assays, immunohistochemistry, and behavioral techniques to examine the effect and mechanism of captopril on depressive-like behavior in 2 animal models, the chronic unpredictable stress model and the chronic social defeat stress model. RESULTS: Captopril (19.5 or 39 mg/kg, intraperitoneal injection) exerted rapid antidepressant activity in mice treated under the chronic unpredictable stress model and mice treated under the chronic social defeat stress model. Pharmacokinetic analysis revealed that captopril crossed the blood-brain barrier and that lisinopril, another ACEI with better blood-brain barrier permeability, exerted a faster and longer-lasting effect at a same molar equivalent dose. This antidepressant effect seemed to be independent of the renin-angiotensin system, but dependent on the bradykinin (BK) system, since the decreased BK detected in the stressed mice could be reversed by captopril. The hypofunction of the downstream effector of BK, Cdc42 (cell division control protein 42) homolog, contributed to the stress-induced loss of dendritic spines, which was rapidly reversed by captopril via activating the mTORC1 (mammalian target of rapamycin complex 1) pathway. CONCLUSIONS: Our findings indicate that the BK-dependent activation of mTORC1 may represent a promising mechanism underlying antidepressant pharmacology. Considering their affordability and availability, ACEIs may emerge as a novel fast-onset antidepressant, especially for patients with comorbid depression and hypertension.

Structural basis for energy and electron transfer of the photosystem I-IsiA-flavodoxin supercomplex.

Under iron-deficiency stress, which occurs frequently in natural aquatic environments, cyanobacteria reduce the amount of iron-enriched proteins, including photosystem I (PSI) and ferredoxin (Fd), and upregulate the expression of iron-stress-induced proteins A and B (IsiA and flavodoxin (Fld)). Multiple IsiAs function as the peripheral antennae that encircle the PSI core, whereas Fld replaces Fd as the electron receptor of PSI. Here, we report the structures of the PSI3-IsiA18-Fld3 and PSI3-IsiA18 supercomplexes from Synechococcus sp. PCC 7942, revealing features that are different from the previously reported PSI structures, and a sophisticated pigment network that involves previously unobserved pigment molecules. Spectroscopic results demonstrated that IsiAs are efficient light harvesters for PSI. Three Flds bind symmetrically to the trimeric PSI core-we reveal the detailed interaction and the electron transport path between PSI and Fld. Our results provide a structural basis for understanding the mechanisms of light harvesting, energy transfer and electron transport of cyanobacterial PSI under stressed conditions.

[Effects of water vapor source and local environmental factors on the hydrogen and oxygen isotopic compositions of precipitation in Huitong, Hunan Province, China].

Deuterium (D) and oxygen-18 (18O) are common environmental tracers in water. Understanding the isotopic compositions of precipitation is necessary for further studies on local and global water cycling processes. To reveal the mechanism of isotopic compositions of precipitation in subtropical monsoon region in response to environmental changes, we collected 49 precipitation samples and recorded related environmental factors from May 2017 to August 2019 in Huitong field station of Chinese Academy of Sciences in Hunan Province. We analyzed the temporal variations in D and 18O values in precipitation and analyzed the influence of water vapor source and local environmental factor on stable isotopic compositions of precipitation. The local meteoric water line was established as δD=(7.45±0.17)δ18O+(10.10±1.25) (R2=0.93, P<0.01), the slope of which was slightly lower than China's meteoric water line and the global meteoric line. The D and 18O values of precipitation samples were closely coupled with local meteorological conditions and dominant moisture sources. The 18O and D contents were depleted during summer monsoon season but enriched during winter monsoon season. During the summer monsoon and post-monsoon seasons, precipitation in this area came mainly from the Bay of Bengal, the South China Sea, and the West Pacific at three different types of air pressure, which lead to the similarity of the D-excess value of the precipitation to global average. The lower intercept of meteoric water line and the higher D-excess value for precipitation during the winter monsoon season resulted from moisture from remote westerly air masses, degenerated tropical marine air masses from the Bay of Bengal, and inland moisture in the pre-monsoon period, which were also affected by local environmental factors.

Activation of AMPK-dependent autophagy in the nucleus accumbens opposes cocaine-induced behaviors of mice.

Cocaine is a strong central nervous system stimulant, which can induce drug addiction. Previous studies have reported that cocaine-induced autophagy is involved in neuroinflammation and cell death. However, the role of autophagy in psychomotor sensitivity to cocaine has not been explored. Here, we reported that D1 receptor -CaMKII-AMPK-FoxO3a signaling pathway was involved in acute cocaine application-induced autophagy in the nucleus accumbens (NAc) both in vitro and in vivo. Furthermore, we found that knockdown of the ATG5 gene in the NAc augmented behavioral response to cocaine, and induction of autophagy in the NAc with rapamycin attenuated cocaine-induced behavioral response, which was coincident with the alterations of dendritic spine density in neurons of NAc. These results suggest that cocaine exposure leads to the induction of autophagy, which is a protective mechanism against behavioral response to cocaine of male mice.