The role of NMDA receptors in rat propofol self-administration.

BACKGROUND: Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators neural plasticity, neuronal development, addiction, and neurodegeneration. In the present study, we explored the role of these receptors in the context of rat propofol self-administration. METHODS: Sprague-Dawley Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using a fixed-ratio (FR) schedule over the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, followed 10 min later by a propofol self-administration session. RESULTS: After training, rats successfully underwent acquisition of propofol self-administration, as evidenced by a significant and stable rise in the number of active nose-pokes resulting in propofol administration relative to the number of control inactive nose-pokes (P < 0.01). As compared to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited a significantly greater number of propofol infusions (F (3, 28) = 4.372, P < 0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg of this compound. In addition, MK-801 failed to alter the numbers of active (F (3, 28) = 1.353, P > 0.05) or inactive (F (3, 28) = 0.047, P > 0.05) responses in these study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg MK-801 (P = 0.006, P < 0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group displayed a significant reduction in the number of active nose-poke responses (F (3, 20) = 20.8673, P < 0.01) and the number of sucrose pellets (F (3, 20) = 23.77, P < 0.01), while their locomotor activity was increased (F (3, 20) = 22.812, P < 0.01). CONCLUSION: These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.

Differential involvement of GABAA and GABAB receptors in propofol self-administration in rats.

AIM: Propofol has shown abuse potential. The aim of the present study is to investigate the effects of GABA(A) antagonist and GABA(B) agonist on propofol reinforcement. METHODS: Sprague-Dawley rats were trained to self-administer propofol at a dose of 1.7 mg/kg per infusion under a fixed ratio (FR1) schedule of reinforcement for 14 d. In a separate set of experiments, food-maintained self-administration under a fixed ratio (FR5) schedule and locomotor activities of Sprague-Dawley rats were examined. RESULTS: GABA(A) receptor antagonist bicuculline (0.25 mg/kg, ip) significantly increased the number of injections and active responses. Pretreatment with GABA(B) receptor agonist baclofen (3 mg/kg, ip) significantly decreased the number of active responses and total infusions of propofol during the training session. Moreover, microinjection of baclofen (50 and 100 ng/side) into the ventral tegmental area (VTA) significantly decreased the number of active responses and total infusions of propofol. Neither baclofen (1-3 mg/kg, ip) nor bicuculline (0.25-1 mg/kg, ip) affected food-maintained responses or motor activities. CONCLUSION: Propofol maintains its reward properties partially through GABA(A) receptor activation. Stimulation of GABA(B) receptors in VTA may counteract the reinforcing properties of propofol.

[Analgesic and sedative effects of multimodal analgesia in stage of emergence after general anesthesia for cleft lip and/or palate prosthesis].

OBJECTIVE: To investigate the effects of multimodal analgesia on analgesia and sedation during emergence of general anesthesia for cleft lip and/or palate surgery pediatric patients. METHODS: Fifty-four pediatric patients with ASA I and II cleft lip and/or palate, aged 2-7, undergoing prosthesis were randomly allocated into 2 groups: control group (Group C, n=28) inhaling nitrous oxide/oxygen (50%:50%) and sevoflurane(5%) for general anesthesia, and multimodal group (Group M, n=26), injected intravenously with fentanyl and atracurium in addition to inhalation of nitrous oxide/oxygen (50%:50%) and sevoflurane (5%). Ventilation was controlled with PCV modal to maintain end-tidal CO2 to 35-45 mmHg. Local anesthesia at the surgical site was facilitated by the surgeon before the beginning of surgery. After intubation, rectal paracetamol was used for Group M (120 mg for 2-4 year-olds and 325 mg for 5-7 year-olds) and fentanyl 0.5 microg/kg was injected for postoperative analgesia 10 min before the end of surgery. An observer who was blinded to the protocol recorded the time from the discontinuation of sevoflurane and nitrous oxide to tracheal extubation, accessed the sedation and pain scale, recorded the time ready for discharge from post-anesthesia care unit (PACU) and the incidence of adverse effects. RESULTS: The time ready for discharge from PACU of Group M was (25+/-4) min, significantly shorter than that of Group C [(32+/-3) min, t=7.426, P<0.01]. The analgesia satisfaction rate of Group M was 69.2% (18/26), significantly higher than that of Group C [25.0%, 7/28, P<0.05]. The severe pain rate of Group M was 7.7%, significantly lower than that of Group C (35.7%, F=5.333, P=0.021). The agitation rate of Group M was 11.5%, significantly lower than that of Group C (39.3%, F=4.571, P=0.033). CONCLUSION: Multimodal analgesic regimen of infiltration of local anesthetic at surgical site and rectal paracetamol and intravenous fentanyl provides sufficient analgesia, minimizes the incidence of agitation after general anesthesia in cleft lip and/or palate surgery for children, increases the speed of referring patients in PACU, and ensures the safety of the postanaesthetic patients.

In vitro assessment of 24 CYP2D6 allelic isoforms on the metabolism of methadone.

CYP2D6 is an important member of the cytochrome P450 (CYP450) enzyme super family, with at least 100 CYP2D6 alleles being previously identified. Genetic polymorphisms of CYP2D6 significantly influence the efficacy and safety of some drugs, which might cause adverse effects and therapeutic failure. The aim of this study was to clarify the catalytic activities of 24 CYP2D6 alleles on the oxidative in vitro metabolism of methadone. Reactions were incubated with 50-2000 µM methadone for 30 min at 37 °C and terminated by cooling to -80 °C immediately. Methadone and the major metabolite EDDP were analyzed by an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) system. Compared with wild-type CYP2D6*1, most variants showed significantly altered values in Vmax and intrinsic clearance (Vmax /Km ). Only three variants (CYP2D6*88, *91 and E215K) exhibited markedly increased intrinsic clearance values, and one variant CYP2D6*94 showed no significant difference. On the other hand, the kinetic parameters of two CYP2D6 variants (CYP2D6*92 and *96) could not be determined because they had no detectable enzyme activity, whereas 18 variants exhibited significantly decreased values. To sum up, this study demonstrated that more attention should be paid in clinical administration of methadone to individuals carrying these CYP2D6 alleles. Copyright © 2016 John Wiley & Sons, Ltd.

[Study on HPLC fingerprint of Xuelian injection].

OBJECTIVE: To establish the HPLC fingerprint of Xuelian injection. METHOD: HPLC with Diamonsil C18 (4.6 mm x 250 mm, 5 microm) column was used, the methanol-1% acetic acid as a mobile phase and detection wavelength at 270 nm. RESULT: Indicating 11 peaks on HPLC fingerprint. CONCLUSION: This method is simple and acurate with a good reproducibility and can be used as a quality control method for Xuelian injection.

[Effects of electroacupuncture on bispectral index and plasma beta-endorphin in patients undergoing colonoscopy].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on bispectral index (BIS) and plasma beta-endorphin (beta-EP) level in patients undergoing colonoscopy. METHODS: Sixty patients were equally randomized into EA group and control group with 30 cases in each. EA (2 Hz/100 Hz, 4-6 V) was applied to the right Zusanli (ST 36) and Shangjuxu (ST 37), and the left Yinlingquan (SP 9), Sanyinjiao (SP 6) and bilateral Hegu (LI 4) respectively 30 min before colonoscopy. The mean arterial pressure (MAP), heart rate (HR) and BIS in two groups were continuously monitored during the study. Plasma beta-EP concentration was detected by radioimmunoassay. The patient's adverse reactions (including pain, satisfaction degree, etc.) were evaluated by visual analog scale (VAS) and verbal stress scale (VSS). RESULTS: Self-comparison showed that MAP and HR in control group increased significantly during colonoscope's splenic flexure passing (P<0.05). Whereas the 2 indexes in EA group had no significant changes during colonoscope insertion, and its splenic flexure passing, hepatic flexure passing and post-enteroscopy (P>0.05). Comparison between two groups showed that MAP at the time-point of colonoscope insertion, and HR at the time-point of colonoscope's splenic flexure passing in EA group were significantly lower than those in control group (P<0.05). BIS values of EA group were significantly lower than those of control group at different time-points after colonoscope insertion (P<0.01). Plasma beta-EP concentrations at the time-points of colonoscope's hepatic flexure passing and post-enteroscopy were evidently increased in both groups in comparison with pre-enteroscopy (P<0.01), and beta-EP was significantly lower in EA group than that in control group at the time-point of colonoscope's hepatic flexure passing (P<0.05). The dosage of Midazolam used for conscious-sedation and the scores of VAS and VSS were also considerably lower in EA group than those in control group (P<0.05, P<0.01). No significant differences were found between two groups in the adverse reactions as dizziness, nausea, vomiting and abdominal pain, but the patients' satisfaction degree in EA group was evidently higher than that in control group (P<0.05). CONCLUSION: Acupuncture analgesia can effectively lower the colonoscopy patients' BIS value and plasma beta-EP level, meaning attenuation of the patients' stress responses during colonoscopy after EA.