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The Taffe Laboratory

Research

Research in the Taffe Laboratory focuses on brain substrates which subserve cognitive function and complex behavior. Ongoing efforts in the laboratory study the etiology of cognitive dysfunction associated with exposure to drugs of abuse.

Cognitive Effects of Exposure to Abused Drugs

Individuals who ingest recreational drugs have been shown to exhibit a number of cognitive or behavioral impairments. Conclusive linking of such behavioral problems to a specific drug or pattern of chronic use is complicated by the fact that most drug users have substantial rates of exposure to multiple drugs concurrently and across time. In particular, exposure to alcohol, delta-9-tetrahydrocannabinol (THC) and nicotine is common in users of most other drugs. Furthermore, it is impossible to demonstrate that cognitive performance levels in recreational users are not merely a reflection of pre-existing group differences. Thus animal models are necessary to demonstrate a causal relationship between a specific pattern of drug exposure and the observed behavioral or cognitive impairment.

Projects in the laboratory focus on the acute and lasting effects of exposure to stimulants such as d-methamphetamine,  3,4-methylenedioxymethamphetamine (MDMA, or "Ecstasy") and the emerging, novel substituted cathinone stimulants (often termed "bath salts" in popular media).  We are also investigating the manner by which chronic alcohol drinking in adolescent animals leads to disruption of spatial memory and several executive functions. Our participation in the Translational Center on the Clinical Neurobiology of Cannabis Addiction led to investigation of the cognitive and behavioral effects of exposure to THC in adolescent monkeys .

Wright, Jr, M.J., Vandewater, S.A., Angrish, D., Dickerson, T.J. and Taffe, M.A. Mephedrone (4-methylmethcathinone, 4MMC) and d-methamphetamine improve visuo-spatial associative memory, but not spatial working memory, in rhesus macaques, British Journal of Pharmacology, 2012, 167(6):1342-1352. [ PubMed Abstract ][ Publisher Link ]

Wright, Jr., M.J., Glavis-Bloom, C. and Taffe, M.A. Acute ethanol reduces reversal cost in discrimination learning by reducing perseverance in adolescent rhesus macaques, ACER, 2013, in press

Wright, Jr, M.J., Vandewater, S.A., Parsons, L.H. and Taffe, M.A. Δ9tetrahydrocannabinol impairs reversal learning but not extra-dimensional shifts in rhesus macaques. Neuroscience, 2013 Apr 3;235:51-8. doi: 10.1016/j.neuroscience.2013.01.018. Epub 2013 Jan 16.

Substance Abuse Therapy

Methamphetamine Addiction: 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. 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. The studies currently underway will create candidate active vaccines specific for METH (MCV) and evaluate the most promising candidates in a cascade of in vivo models.

Miller, M.L., Moreno, A.Y., Aarde, S.M., Creehan, K.M., Vandewater, S.A., Vaillancourt, B.D., Wright, Jr., M.J., Janda, K.D. and Taffe, M.A. A methamphetamine vaccine attenuates methamphetamine-induced disruptions in thermoregulation and activity in rats, Biological Psychiatry, 2013 Apr 15;73(8):721-8. doi: 10.1016/j.biopsych.2012.09.010. Epub 2012 Oct 23. [ PubMed ] [Publisher Link]

Physical Exercise: Epidemiological evidence shows that adolescents and adults who are involved in consistent vigorous exercise may be at reduced risk of recreational drug use. However social contexts that influence both exercise and drug taking make it difficult, if not impossible, to infer a specific protective effect. Our studies attempt to model different ways in which physical exercise may influence drug taking using rat intravenous self-administration and activity wheel models.

Miller, M.L., Vaillancourt, B.D., Wright Jr., M.J., Aarde, S.M., Vandewater, S.A., Creehan, K.M. and Taffe, M.A. Reciprocal inhibitory effects of intravenous d-methamphetamine self-administration and wheel activity in rats, 2012, Drug Alcohol Depend, 121:90-96 2011 Sep 5. [Epub ahead of print] [ PubMed Abstract ] [ Publisher Link ][ RequestPDF ]

The Taffe Laboratory is supported by USPHS Grants R01 DA024105, R01 DA024705 and R01 AA016807

Previous work has been supported by USPHS grants P20 DA024194, P60 AA006420, R01 DA18418, R21 AA013972, R01 DA13390, R01 MH61692 and P30 MH62261.