Drug addiction,also referred to as drug dependence or substance use disorder,is a chronic and recurrent brain disease.Its main characteristics are compulsive drug-seeking behavior,continued use of drugs,and a loss of control over intake.Prolonged use of addictive substances can result in both physiological and psychological dependence.When usage is ceased,individuals may experience intense discomfort,including anxiety,insomnia,nausea,vomiting,and a strong craving for the substances.Drug dependence is classified into two types:physical dependence and psychological dependence.Physical dependence describes a pathological state of adaptation that results from the repeated use of addictive substances,leading to severe withdrawal syndrome upon cessation.Psychological dependence involves a mental craving for addictive substances,which is needed to experience the specific euphoria that follows consumption.Regular or continuous use is required to sustain these euphoric effects.The mechanisms of addiction are complex and influenced by genetic,environmental,and various other factors.They involve higher-level neurological activities,such as memory,reward,and decision-making.Currently,effective treatment methods for drug addiction are insufficient.Due to the complexity of drug addiction,laboratory animal research is essential.Using animal behavioral models to simulate human drug addiction can enhance our understanding of the mechanisms of addiction.This research offers a comprehensive overview of various animal experimental models that explore both physical and psychological dependence.It includes detailed descriptions of the methods and procedures used to assess physical dependence,behavioral sensitization,conditioned place preference,drug discrimination,and self-administration experiments.Additionally,the characteristics of each experimental model are compared,and the relevance of these models is discussed,aiming to provide support for the research on addiction mechanisms and the development of therapeutic methods.

Drug addiction,also referred to as drug dependence or substance use disorder,is a chronic and recurrent brain disease.Its main characteristics are compulsive drug-seeking behavior,continued use of drugs,and a loss of control over intake.Prolonged use of addictive substances can result in both physiological and psychological dependence.When usage is ceased,individuals may experience intense discomfort,including anxiety,insomnia,nausea,vomiting,and a strong craving for the substances.Drug dependence is classified into two types:physical dependence and psychological dependence.Physical dependence describes a pathological state of adaptation that results from the repeated use of addictive substances,leading to severe withdrawal syndrome upon cessation.Psychological dependence involves a mental craving for addictive substances,which is needed to experience the specific euphoria that follows consumption.Regular or continuous use is required to sustain these euphoric effects.The mechanisms of addiction are complex and influenced by genetic,environmental,and various other factors.They involve higher-level neurological activities,such as memory,reward,and decision-making.Currently,effective treatment methods for drug addiction are insufficient.Due to the complexity of drug addiction,laboratory animal research is essential.Using animal behavioral models to simulate human drug addiction can enhance our understanding of the mechanisms of addiction.This research offers a comprehensive overview of various animal experimental models that explore both physical and psychological dependence.It includes detailed descriptions of the methods and procedures used to assess physical dependence,behavioral sensitization,conditioned place preference,drug discrimination,and self-administration experiments.Additionally,the characteristics of each experimental model are compared,and the relevance of these models is discussed,aiming to provide support for the research on addiction mechanisms and the development of therapeutic methods.

Salicylate 2-O-β-d-glucoside (SAG) is a derivative of salicylate in plants. Recent reports showed that SAG could be considered as a potential anti-inflammatory substance due to its anti-inflammatory and analgesic effects, and less irritation compared with salicylic acid and aspirin. The biological method uses renewable resources to produce salicylic acid compounds, which is more environmentally friendly than traditional industry methods. In this study, Escherichia coli Tyr002 was used as the starting strain, and a salicylic acid producing strain of E. coli was constructed by introducing the isochorismate pyruvate lyase gene pchB from Pseudomonas aeruginosa. By regulating the expression of the key genes in the downstream aromatic amino acid metabolic pathways, the titer of salicylic acid reached 1.05 g/L in shake flask fermentation. Subsequently, an exogenous salicylic acid glycosyltransferase was introduced into the salicylic acid producing strain to glycosylate the salicylic acid. The newly engineered strain produced 5.7 g/L SAG in shake flask fermentation. In the subsequent batch fed fermentation in a 5 L fermentation tank, the titer of SAG reached 36.5 g/L, which is the highest titer reported to date. This work provides a new route for biosynthesis of salicylate and its derivatives.
Escherichia coli/genetics* ; Glucosides ; Metabolic Engineering ; Salicylic Acid ; Pyruvic Acid

This paper presents a microcontroller system for target controlled infusion according to pharmacodynamic parameters of intravenous anesthetics. It can control the depth of anesthesia by adjusting the level of plasma concentrations. The system has the advantages of high precision, extending power and easy manipulation. It has been used in the clinical anesthesia.
Anesthesia, Intravenous ; instrumentation ; methods ; Anesthetics, Intravenous ; administration & dosage ; pharmacokinetics ; Drug Delivery Systems ; methods ; Drug Therapy, Computer-Assisted ; methods ; Humans ; Monitoring, Intraoperative ; methods

OBJECTIVE　To establish an assay for the simultaneous determination of propofol and lidocaine in human plasma using reversed-phase high performance liquid chromatography（RP-HPLC）.METHODS　With thymol and bupivacaine as the internal standards for propofol and lidocaine respectively,the extraction was performed with cyclohexane.The organic layer was evaporated and the residue was redissolved by mobile phase.The concentrations of propofol and lidocaine were assayed on a hypersil BDS C18 column with a mobile phase consisting of acetonitrile-methanol-water（10∶60∶30）（including 0.14% n-butyamine 0.1% acetic acid）at a flow rate of 1 mL*min-1 and detected at 220 nm during 1～7 min and at 273 nm during 7～16 min.RESULTS　The linearity between concentrations and peak area ratio was obtained from 0.1 μg*mL-1 to 25.6 μg*mL-1（r=0.998，r=0.9995）.The detection limits were 0.1 μg*mL-1 for propofol and 0.05 μg*mL-1 for lidocaine.The within-day and between-day variation coefficients were less than 5%(n=5).The average recoveries were 93.33%,99.4% and 90%,95.67% respectively.CONCLUSION　The method was found to be rapid,accurate and precise.It is suitable for clinical pharmacokinetic and pharmacodynamic study.

Objective: To perform target-controlled infusion (TCI) in total intravenous anesthesia (TIVA) of propofol and fentanyl. Method: Using effect compartment modeling, computer controlled infusion(the computer software was developed by Coezee and Pina) was performed during induction and maintenance of anesthesia in two groups of adult patients. The target predicted concentration of theoretical effect-site compartment for propofol was 4?g/ml and for fentanyl was 2?g/ml. The plasma concentration (Cm) of propofol was determined by fluorospectrophotometry and Cm of fentanyl was measured with radioimmunoassay. Result: The mean Cm from 0 to 120 min showed that excessive dose of propofol was administered, MDAPE=25%,however the mean Cm of fentanyl was lower than the target level obviously,MDAPE=35.5% in first group. After an imitative calculation,another pharmacokinetic (PK) parameter sets of propofol and fentanyl were selected in the second group,MDAPE=15.5% for propofol and MDAPE=37. 75% for fentanyl. Conclusion: The concentrations of propofol and fentanyl in the effect site compartment can be achieved rapidly by using the effect compartment control algorithm. The PK parameter,described by different authors influences the accuracy of TCI administration.

To study the effects of fentanyl on the MAC of sevoflurane. Method: One hundred and sixteen patients were given continuous infusion of fentanyl with CACI-pump (computer-assisted continuous infusion)to maintain different target plasma concentrations (Ct), meanwhile inhaled sevoflurane. All patients were randomly divided into seven groups receiving sevoflurane in oxygen with fentanyl target plasma concentration of 0?g/L (n=16), 0.5?g/L(n=20), 1?g/L(n=18), 2?g/L(n=16), 3?g/L(n=18), 4?g/L(n= 14) or 6?g/L(n= 14). Plasma concentraion of fentanyl was measured with radioimmunoassay. MAC determination, in response to the stimulus of skin incision, was made using the "up-down" method and logistic regression. Result: The MAC of sevoflurane from group 1 to group 7 were 1.94%, 1.89%, 1.55%, 1.29%, 1.09%, 0.86% and 0.35% respectively. Conclusion: We verify the MAC of sevoflurane, which is reduced by increasing plasma fentanyl concentration.

Objective To study the influence of lidocaine on the propofol concentration effect relationships for loss of eyelash reflex and loss of consciousness,hemodynamic function Methods Thirty eight patients were randomly allocated to receiving a computer controlled infusion of lidocaine at target concentration of 0?g?ml -1 (group A,n=9),1 25?g?ml -1 (group B,n=7), 2 5?g?ml -1 (group C,n=7), 5?g?ml -1 (group D,n=8),or 7?g?ml -1 (group E,n=7) respectively While the target concentration of lidocaine was kept stable, propofol was administrated with a computer controlled infusion at an initial target concentration of 0 5 1?g?ml -1 , which was increased every time by 0 5?g?ml -1 until loss of consciousness Plasma concentrations of lidocaine and propofol were measured with high performance liquid chromatography Results 50% of patients lost eyelash reflex and consciousness at plasma propofol concentrations(Cp50) of 1 78 and 3 17?g?ml -1 in the absence of lidocaine In the presence of plasma lidocaine concentration of 1 25 4 3 ?g?ml -1 ,the Cp50 for loss of eyelash reflex was reduced by 42 1% There was a linear regression relationship between plasma lidocaine concentrations from 0 to 7?g?ml -1 and the Cp50 for loss of consciousness (r=-0 69 ) Conclusions The Chinese Cp50 for loss of eyelash reflex and consciousness are lower than those reported abroad Plasma lidocaine concentration at 4?g?ml -1 can potentiate properly the potency of propofol on the sedation and hypnosis during anesthesia induction

Objective To study the influence of age on the pharmacodynamics of propofol including the relationship between plasma concentrations of propofol and the time of loss of consciousness or return of consciousness.Methods Forty-two ASAⅠ-Ⅱ patients were assigned to one of three age groups: group A: age ranged from 18-34 yr(n=14); group B:35-60 yr(n=15); and group C: 61-90 yr(n=13). Once spinal anesthesia was completed, propofol infusion at the rate of 0.5 mg?kg -1?min -1(group A) or 0.4 mg?kg -1?min -1(group B and C )was started until burst suppression of EEG lasting 3s was observed. Venous blood samples were taken at 1, 2, 4, 8,10, 15, 30, 45,60,90,120 and 240 min after the start of propofol infusion for the determination of plasma propofol concentrations. The influence of age on relationship between propofol plasme concentration and loss of consciousness or return of consciousness was analyzed by non-linear regression. The relationships between age and time of loss of consciousness,duration of sleep,the total dose of propofol,the plasma concentration at the time of loss of consciousness or return of consiousness were determined by linear regression.Results As compared with those in group A and B,the time of loss of consciousness and the total dose of propofol required decreased markedly in group C. The observation showed increased sensitivity to propofol in elderly patients. The EC50 values for loss of consciousness were 2.86 (at age of 25 yr),2.26 (at 50yr), and 1.78 (at 75yr) ?g?ml -1,and the EC50 values for return of consciousness of 1.76 (at 25 yr),1.45(at 50yr),1.11(at 75yr)?g?ml -1 respectively.Conclusions Elderly patients are more sensitive to propofol than younger people in terms of hypnosis and EEG effects.