The abuse of, and addiction to, d-methamphetamine (METH) interferes with many aspects of personal health, vocational performance, interpersonal relationships and financial well being. Behavioral consequences of METH abuse and the METH trade also strain legal and emergency medical resources throughout the US. METH is therefore a significant and continuing public health concern. Current therapeutic approaches for METH addiction are less than completely effective and no approved pharmacotherapies for METH addiction exist. Recent successes in early clinical trials using immunotherapeutic approaches for cocaine and nicotine addiction have motivated interest in creating similar approaches for methamphetamine addiction. Work under the initial funding interval of this project has created the MH6 vaccine which was shown to generate antibodies which sequester METH in the blood. The vaccine also attenuated METH effects on locomotor activity, thermoregulation and intravenous self-administration of METH. New studies seek to optimize the vaccine for higher antibody titer by determining effects of different carrier proteins and adjuvants. Studies in rats will use converging models of drug-related reward, including intracranial self-stimulation reward and the dopamine response in the nucleus accumbens shell, to determine how the vaccine alters the acquisition of self- administration. Additional work will determine if an optimized vaccine can prevent the escalation to unregulated METH intake using a long-access procedure and if the vaccine can reverse an established self-administration pattern. Together these studies will make significant progress on optimizing both the design and likely translational application of an anti-METH vaccine.
Methamphetamine (METH) abuse and dependence continues to be a significant problem for personal health and well-being as well as a challenge for public health and law enforcement. Current treatment options for substance abuse have limited effect but recent vaccination strategies have shown promise. Thus the proposed studies to generate vaccines against METH have the potential to improve the treatment of METH addiction.
|Aarde, S M; Huang, P K; Dickerson, T J et al. (2015) Binge-like acquisition of 3,4-methylenedioxypyrovalerone (MDPV) self-administration and wheel activity in rats. Psychopharmacology (Berl) 232:1867-77|
|Miller, Michelle L; Moreno, Amira Y; Aarde, Shawn M et al. (2013) A methamphetamine vaccine attenuates methamphetamine-induced disruptions in thermoregulation and activity in rats. Biol Psychiatry 73:721-8|
|Aarde, Shawn M; Angrish, Deepshikha; Barlow, Deborah J et al. (2013) Mephedrone (4-methylmethcathinone) supports intravenous self-administration in Sprague-Dawley and Wistar rats. Addict Biol 18:786-99|
|Miller, M L; Creehan, K M; Angrish, D et al. (2013) Changes in ambient temperature differentially alter the thermoregulatory, cardiac and locomotor stimulant effects of 4-methylmethcathinone (mephedrone). Drug Alcohol Depend 127:248-53|
|Aarde, S M; Huang, P K; Creehan, K M et al. (2013) The novel recreational drug 3,4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: self-administration and locomotor activity in rats. Neuropharmacology 71:130-40|
|Miller, M L; Vaillancourt, B D; Wright Jr, M J et al. (2012) Reciprocal inhibitory effects of intravenous d-methamphetamine self-administration and wheel activity in rats. Drug Alcohol Depend 121:90-6|
|Moreno, Amira Y; Janda, Kim D (2011) Current challenges for the creation of effective vaccines against drugs of abuse. Expert Rev Vaccines 10:1637-9|
|Moreno, Amira Y; Mayorov, Alexander V; Janda, Kim D (2011) Impact of distinct chemical structures for the development of a methamphetamine vaccine. J Am Chem Soc 133:6587-95|
|Gilpin, N W; Wright Jr, M J; Dickinson, G et al. (2011) Influences of activity wheel access on the body temperature response to MDMA and methamphetamine. Pharmacol Biochem Behav 99:295-300|