Limits...
A conjugate vaccine attenuates morphine- and heroin-induced behavior in rats.

Li QQ, Sun CY, Luo YX, Xue YX, Meng SQ, Xu LZ, Chen N, Deng JH, Zhai HF, Kosten TR, Shi J, Lu L, Sun HQ - Int. J. Neuropsychopharmacol. (2014)

Bottom Line: The effects of the vaccine on the morphine-induced elevation of dopamine levels in the nucleus accumbens were determined by high-performance liquid chromatography.The vaccine significantly prevented the elevation of dopamine levels in the nucleus accumbens induced by a single morphine challenge.These results demonstrate that active immunization with the present vaccine induces a robust morphine/heroin-specific antibody response in rats and attenuates the behavioral effects of morphine and heroin.

View Article: PubMed Central - PubMed

Affiliation: Peking University Sixth Hospital/Institute of Mental Health (Dr Li, Ms C.-Y. Sun, Dr Luo, Ms Meng, Mr Xu, Ms Deng, Drs Lu, and H.-Q. Sun), and National Institute on Drug Dependence, Peking University, Beijing, China (Drs Dr Li, Ms C.-Y. Sun, Dr Luo, Dr Xue, Ms Meng, Mr Xu, Ms Chen, Ms Deng, Drs Zhai, Shi, and Lu); Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control, Beijing, China (Dr Li); Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China (Drs Lu and H.-Q. Sun); Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas (Dr Kosten).

Show MeSH

Related in: MedlinePlus

Preparation of morphine-N-(ε-trifluoroacetylcaproyloxy) succinimide ester (TFCS)-keyhole limpet hemocyanin (KLH), showing conjugation of 6-glutarylmorphine (M-6-G) to KLH via a TFCS-derived linker composition. Structures 1 and 2 represent M-6-G and morphine-TFCS-KLH, respectively.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4376548&req=5

Figure 1: Preparation of morphine-N-(ε-trifluoroacetylcaproyloxy) succinimide ester (TFCS)-keyhole limpet hemocyanin (KLH), showing conjugation of 6-glutarylmorphine (M-6-G) to KLH via a TFCS-derived linker composition. Structures 1 and 2 represent M-6-G and morphine-TFCS-KLH, respectively.

Mentions: For the preparation of morphine-TFCS-KLH, KLH was dissolved in 0.01M phosphate-buffered saline (PBS), pH 7.2. TFCS (weight ratio 10:1 to KLH) was dissolved in 20% dimethylsulfoxide in distilled water and immediately added to the KLH solution, followed by incubation at 25ºC for 12 hours. NaOH solution (1M) was then added to adjust the pH to 8.1 to 8.5, and the solution was incubated at 25ºC for 3 hours. The solution was then dialyzed at 4ºC for 24 hours to yield KLH-TFCS moiety. Afterward, 100mg M-6-G and 100mg 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC; Sigma-Aldrich, St. Louis, MO) were dispersed in 100mL distilled water, pH 5.5, and stirred at 37ºC for 2 hours to yield EDC-M-6-H derivative (135mg). The EDC-M-6-H derivative (weight ratio 5:1 to KLH-TFCS moiety) was immediately mixed with KLH-TFCS moiety in 100mL PBS (pH 7.5) and stirred at 25ºC for 12 hours. The reaction mixture was purified by dialysis in PBS (pH 7.5) at 4ºC for 48 hours and then concentrated by pressure dialysis and freeze-drying for 24 to 48 hours to yield morphine-TFCS-KLH (Figure 1).


A conjugate vaccine attenuates morphine- and heroin-induced behavior in rats.

Li QQ, Sun CY, Luo YX, Xue YX, Meng SQ, Xu LZ, Chen N, Deng JH, Zhai HF, Kosten TR, Shi J, Lu L, Sun HQ - Int. J. Neuropsychopharmacol. (2014)

Preparation of morphine-N-(ε-trifluoroacetylcaproyloxy) succinimide ester (TFCS)-keyhole limpet hemocyanin (KLH), showing conjugation of 6-glutarylmorphine (M-6-G) to KLH via a TFCS-derived linker composition. Structures 1 and 2 represent M-6-G and morphine-TFCS-KLH, respectively.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4376548&req=5

Figure 1: Preparation of morphine-N-(ε-trifluoroacetylcaproyloxy) succinimide ester (TFCS)-keyhole limpet hemocyanin (KLH), showing conjugation of 6-glutarylmorphine (M-6-G) to KLH via a TFCS-derived linker composition. Structures 1 and 2 represent M-6-G and morphine-TFCS-KLH, respectively.
Mentions: For the preparation of morphine-TFCS-KLH, KLH was dissolved in 0.01M phosphate-buffered saline (PBS), pH 7.2. TFCS (weight ratio 10:1 to KLH) was dissolved in 20% dimethylsulfoxide in distilled water and immediately added to the KLH solution, followed by incubation at 25ºC for 12 hours. NaOH solution (1M) was then added to adjust the pH to 8.1 to 8.5, and the solution was incubated at 25ºC for 3 hours. The solution was then dialyzed at 4ºC for 24 hours to yield KLH-TFCS moiety. Afterward, 100mg M-6-G and 100mg 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC; Sigma-Aldrich, St. Louis, MO) were dispersed in 100mL distilled water, pH 5.5, and stirred at 37ºC for 2 hours to yield EDC-M-6-H derivative (135mg). The EDC-M-6-H derivative (weight ratio 5:1 to KLH-TFCS moiety) was immediately mixed with KLH-TFCS moiety in 100mL PBS (pH 7.5) and stirred at 25ºC for 12 hours. The reaction mixture was purified by dialysis in PBS (pH 7.5) at 4ºC for 48 hours and then concentrated by pressure dialysis and freeze-drying for 24 to 48 hours to yield morphine-TFCS-KLH (Figure 1).

Bottom Line: The effects of the vaccine on the morphine-induced elevation of dopamine levels in the nucleus accumbens were determined by high-performance liquid chromatography.The vaccine significantly prevented the elevation of dopamine levels in the nucleus accumbens induced by a single morphine challenge.These results demonstrate that active immunization with the present vaccine induces a robust morphine/heroin-specific antibody response in rats and attenuates the behavioral effects of morphine and heroin.

View Article: PubMed Central - PubMed

Affiliation: Peking University Sixth Hospital/Institute of Mental Health (Dr Li, Ms C.-Y. Sun, Dr Luo, Ms Meng, Mr Xu, Ms Deng, Drs Lu, and H.-Q. Sun), and National Institute on Drug Dependence, Peking University, Beijing, China (Drs Dr Li, Ms C.-Y. Sun, Dr Luo, Dr Xue, Ms Meng, Mr Xu, Ms Chen, Ms Deng, Drs Zhai, Shi, and Lu); Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control, Beijing, China (Dr Li); Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China (Drs Lu and H.-Q. Sun); Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas (Dr Kosten).

Show MeSH
Related in: MedlinePlus