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αPVP and MDPV Active Vaccine Attenuates Wheel Locomotor Behavior Brent R. Kisby1, Michael A. Taffe1 There have been several studies in the efficacy of different vaccines to treat the abuse of methamphetamine (Miller, M et al 2015; 2013), cocaine (Carrera MR et al 2000), and heroin (Scholsburg JE et al 2013). Drug Vaccines “Bath Salts” are a group of synthetic cathinones with the phenylethylamine backbone. They are highly potent for both serotonin and dopamine transporters. These synthetic cathinones have been sold under the labels of “plant food”, “lab certified”, “not for human consumption” and “bath salts”. They also go by the terms “meow meow”, “flakka”, and “monkey dust”. They are sold in headshops and were legal for the longest time because the DEA could not schedule the analogs fast enough. With a slight change in structure as indicated below, each drug has their own properties that are more MDMA-like, cocaine-like, or Methamphetamine-like. unprotected Brain Blood This study was to determine the role of “Bath Salt” vaccine attenuating the stimulant properties of the two synthetic psychostimulants. Methods/Materials • Charles-Rivers Sprague-Dawley (n=36), 76 days old at start of study • Three groups: aPVP vaccine, MDPV vaccine, KLH control Vaccine given at week 0 • Boosted on weeks 2 and 4 • Acute i.p dose of drug (0,.25,.5,1.0,5.0/ mg/kg) with 4 hour run time • Rectal temperature every hour pre-inection and at every hour post initial drug challenge Protected by antibodies Y Vaccine and boost Y Y Y 200 * * 0 2h 3h time Post-Injection 4h KLH-MDPV veh 1400 KLH-MDPV (.25 mg/kg) 1200 KLH-mdpv0.5 1000 800 600 ** 400 200 1h aPVP vac 1400 Y Y Y Y 400 MDPV (5.0 mg/kg) * 800 KLH-mdpv1.0 KLH-mdpv5.0 * 0 Results Y Y Y Y MDPV (1.0 mg/kg) 1000 KLH-MDPV antibody Brain Blood MDPV (0.5 mg/kg) 1200 600 MDPV (veh) MDPV (0.25 mg/kg) 1400 1h Drug molecule Y Wheel Rotations “Bath Salts” are a group of synthetic cathinones with similar psychoactive properties like methamphetamine. The compounds used in this study are MDPV (Methylenedioxypyrovalerone) and aPVP (alpha-pyrrolidinovalerophenone). These compounds are highly potent for the Dopamine transporter and moderately potent for the Serotonin transporter (Simmler et al 2012). “Bath Salts”: Not Really for your Bath MDPV vac Wheel Rotations Introduction Scripps Research Institute, La Jolla, CA 92121 Wheel Rotations 1The 2h 3h time Post-Injection 4h Fig. 3: Total counts of wheel activity (n=12) for MDPV vaccinated animals. αPVP (veh) αPVP (0.25 mg/kg) 1200 αPVP (0.5 mg/kg) 1000 αPVP (1.0 mg/kg) αPVP (5.0 mg/kg) 800 * 600 400 200 Conclusions * • MDPV/aPVP vaccine show efficacy in decreasing the stimulant locomoter effects of both drugs in low to moderate doses, but not the high dose Data mirrors other studies of drug vaccine because there is no protection at the highest dose 0 Adopted from Julian’s Primer of Drug Action © 2014 pg. 230 * 1h 2h 3h time Post-Injection 4h • Dopamine “Bath Salts” MDMA methylone Fig. 1: level of anti-body titer detected by ELISA optical density from rat plasma. The arrows indicate when each rat was boosted with their respective vaccine. Bettween week 6 and week 10 is when the drug study occurred. 4-MMC Cathinone structure 1400 1200 1000 800 600 400 200 0 * ** KLH-aPVP-veh KLH-aPVP0.25 KLH-alpha0.5 KLH-aPVP1.0 KLH-alpha5.0 1. 2. * 3. 4. 5. 1h 2h 3h time Post-Injection 4h Fig. 2: Total counts of wheel activity (n=12) for aPVP vaccinated animals. 5-IT (5-(2-Aminopropyl)indole) methedrone Wheel Rotations KLH-aPVP methcathinone Serotonin (5-HT) 6. Citations Advokat, Claire D., Joseph E. Comaty, and Robert M. Julien. Julien's Primer of Drug Action: A Comprehensive Guide to the Actions, Uses, and Side Effects of Psychoactive Drugs. 13th ed. New York: Worth, 2014. Print. Carrera, M. R. A., J. A. Ashley, B. Zhou, P. Wirsching, G. F. Koob, and K. D. Janda. "Cocaine Vaccines: Antibody Protection against Relapse in a Rat Model." Proceedings of the National Academy of Sciences 97.11 (2000): 6202-206. Web. Miller, Michelle L., Amira Y. Moreno, Shawn M. Aarde, Kevin M. Creehan, Sophia A. Vandewater, Brittani D. Vaillancourt, M. Jerry Wright, Kim D. Janda, and Michael A. Taffe. "A Methamphetamine Vaccine Attenuates Methamphetamine-Induced Disruptions in Thermoregulation and Activity in Rats." Biological Psychiatry 73.8 (2013): 721-28. Web. Miller, M.l., S.m. Aarde, A.y. Moreno, K.m. Creehan, K.d. Janda, and M.a. Taffe. "Effects of Active Anti-methamphetamine Vaccination on Intravenous Self-administration in Rats." Drug and Alcohol Dependence 153 (2015): 29-36. Web. Schlosburg, J. E., L. F. Vendruscolo, P. T. Bremer, J. W. Lockner, C. L. Wade, A. A. K. Nunes, G. N. Stowe, S. Edwards, K. D. Janda, and G. F. Koob. "Dynamic Vaccine Blocks Relapse to Compulsive Intake of Heroin." Proceedings of the National Academy of Sciences 110.22 (2013): 9036-041. Web. Simmler, Ld, Ta Buser, M. Donzelli, Y. Schramm, L-H Dieu, J. Huwyler, S. Chaboz, Mc Hoener, and Me Liechti. "Pharmacological Characterization of Designer Cathinones in Vitro." British Journal of Pharmacology Br J Pharmacol 168.2 (2012): 4 Acknowledgements I would like to thank Michael Taffe for his kind and gracious support and everyone in the Taffe lab for their extensive scientific technical assistance. I would also like to thank Michelle Israel directly and the College of Science co-op advisors for their support. Funding supported by NIDA. www.postersession.com