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

Effects of morphine-N-(ε-trifluoroacetylcaproyloxy) succinimide ester (TFCS)-keyhole limpet hemocyanin (KLH) immunization on morphine-induced locomotor sensitization. (a) Experimental timeline. (b) Initiation of morphine-induced locomotor sensitization. During 14 daily injections of morphine (10mg/kg, s.c.), locomotor activity significantly increased on days 7 and 14 of initiation, with no difference between groups. Locomotor activity on day 0 served as baseline. (c) Locomotor activity in morphine-TFCS-KLH-treated rats was significantly lower compared with KLH-treated rats after the morphine challenge on day 10. (d) Locomotor activity in morphine-TFCS-KLH–treated rats was significantly lower compared with KLH-treated rats after the morphine challenge on day 14. The data are expressed as mean ± SEM. *P < .05, compared with KLH group; **P < .01, compared with KLH group (n=10 per group).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 5: Effects of morphine-N-(ε-trifluoroacetylcaproyloxy) succinimide ester (TFCS)-keyhole limpet hemocyanin (KLH) immunization on morphine-induced locomotor sensitization. (a) Experimental timeline. (b) Initiation of morphine-induced locomotor sensitization. During 14 daily injections of morphine (10mg/kg, s.c.), locomotor activity significantly increased on days 7 and 14 of initiation, with no difference between groups. Locomotor activity on day 0 served as baseline. (c) Locomotor activity in morphine-TFCS-KLH-treated rats was significantly lower compared with KLH-treated rats after the morphine challenge on day 10. (d) Locomotor activity in morphine-TFCS-KLH–treated rats was significantly lower compared with KLH-treated rats after the morphine challenge on day 14. The data are expressed as mean ± SEM. *P < .05, compared with KLH group; **P < .01, compared with KLH group (n=10 per group).

Mentions: The effects of morphine-TFCS-KLH on the psychomotor effect of morphine were determined using a locomotor sensitization model (Figure 5a). During the initiation phase, the analysis revealed a main effect of time (F3,42 = 8.63, P < .001). Locomotor activity significantly increased on day 7 (P < .001, compared with day 0) and day 14 (P < .001, compared with day 0), with no difference between groups (F1,14=0.324, P=.578) (Figure 5b). After the morphine challenge (10mg/kg, s.c.) on day 10 after the fourth immunization, locomotor activity in morphine-TFCS-KLH–treated rats was significantly lower than in the KLH group (F1,14=99.84, P < .05) (Figure 5c, upper), with a significant treatment×time interaction (F7,98=7.88, P < .001) (Figure 5c, lower). Similarly, after the morphine challenge 14 days after the last immunization, locomotor activity was significantly lower in the morphine-TFCS-KLH group (F1,14=149.74, P < .05) (Figure 5d, upper), with a significant treatment×time interaction (F7,98=9.98, P < .001) (Figure 5d, lower). The posthoc analysis revealed a significant difference in locomotor activity between the vaccine and control groups 15 and 30 minutes after both the first and second morphine challenges (all P < .001).


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)

Effects of morphine-N-(ε-trifluoroacetylcaproyloxy) succinimide ester (TFCS)-keyhole limpet hemocyanin (KLH) immunization on morphine-induced locomotor sensitization. (a) Experimental timeline. (b) Initiation of morphine-induced locomotor sensitization. During 14 daily injections of morphine (10mg/kg, s.c.), locomotor activity significantly increased on days 7 and 14 of initiation, with no difference between groups. Locomotor activity on day 0 served as baseline. (c) Locomotor activity in morphine-TFCS-KLH-treated rats was significantly lower compared with KLH-treated rats after the morphine challenge on day 10. (d) Locomotor activity in morphine-TFCS-KLH–treated rats was significantly lower compared with KLH-treated rats after the morphine challenge on day 14. The data are expressed as mean ± SEM. *P < .05, compared with KLH group; **P < .01, compared with KLH group (n=10 per group).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 5: Effects of morphine-N-(ε-trifluoroacetylcaproyloxy) succinimide ester (TFCS)-keyhole limpet hemocyanin (KLH) immunization on morphine-induced locomotor sensitization. (a) Experimental timeline. (b) Initiation of morphine-induced locomotor sensitization. During 14 daily injections of morphine (10mg/kg, s.c.), locomotor activity significantly increased on days 7 and 14 of initiation, with no difference between groups. Locomotor activity on day 0 served as baseline. (c) Locomotor activity in morphine-TFCS-KLH-treated rats was significantly lower compared with KLH-treated rats after the morphine challenge on day 10. (d) Locomotor activity in morphine-TFCS-KLH–treated rats was significantly lower compared with KLH-treated rats after the morphine challenge on day 14. The data are expressed as mean ± SEM. *P < .05, compared with KLH group; **P < .01, compared with KLH group (n=10 per group).
Mentions: The effects of morphine-TFCS-KLH on the psychomotor effect of morphine were determined using a locomotor sensitization model (Figure 5a). During the initiation phase, the analysis revealed a main effect of time (F3,42 = 8.63, P < .001). Locomotor activity significantly increased on day 7 (P < .001, compared with day 0) and day 14 (P < .001, compared with day 0), with no difference between groups (F1,14=0.324, P=.578) (Figure 5b). After the morphine challenge (10mg/kg, s.c.) on day 10 after the fourth immunization, locomotor activity in morphine-TFCS-KLH–treated rats was significantly lower than in the KLH group (F1,14=99.84, P < .05) (Figure 5c, upper), with a significant treatment×time interaction (F7,98=7.88, P < .001) (Figure 5c, lower). Similarly, after the morphine challenge 14 days after the last immunization, locomotor activity was significantly lower in the morphine-TFCS-KLH group (F1,14=149.74, P < .05) (Figure 5d, upper), with a significant treatment×time interaction (F7,98=9.98, P < .001) (Figure 5d, lower). The posthoc analysis revealed a significant difference in locomotor activity between the vaccine and control groups 15 and 30 minutes after both the first and second morphine challenges (all P < .001).

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