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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.

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 .

Neuropharmacology of Drug Addiction

Substituted Cathinone "Bath Salts": A diverse array of new stimulant drugs based on the cathinone core structure emerged on worldwide markets starting around 2008-2009. Early entities included drugs such as 4-methylmethcathinone (4-MMC, mephedrone), 3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxymethcathinone (methylone). Some exhibit neuropharmacological actions similar to MDMA, some are more similar to cocaine and some are more similar to traditional amphetamine stimulants such as methamphetamine. There are now over a dozen cathinone entities which have been placed under Schedule I control by the US DEA, and more of them may follow in an attempt to evade legal control. Our goal with the cathinone project is to determine how the pharmacological differences between these entities confer different risks for compulsive use and for thermoregulatory disruption of a life-threatening nature.

Vandewater, S.A., Creehan, K.M. and Taffe, M.A. Intravenous self-administration of entactogen-class stimulants in male rats. Neuropharmacology, 2015, in press. [ Publisher Site ]

Aarde, S.M., Creehan, K.M., Vandewater, S.A., Dickerson, T.J. and Taffe, M.A. In vivo potency and efficacy of the novel cathinone α-pyrrolidinopentiophenone and 3,4-methylenedioxypyrovalerone: Self-administration and locomotor stimulation in male rats. Psychopharmacology, 2015, 232:3045-3055. [ Publisher Site ][ PubMed ]

Creehan, K.M., Vandewater, S.A. and Taffe, M.A. Intravenous self-administration of mephedrone, methylone and MDMA in female rats. Neuropharmacology, 2015, 92:90-97. [ Publisher Site ][ PubMed ]

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.

Nguyen, J.D., Bremer, P.T., Hwang, C.S., Vandewater, S.A., Collins, K.C., Creehan, K.M., Janda, K.D. and Taffe, M.A. Effective active vaccination against methamphetamine in female rats, Drug Alcohol Depend, 2017, 175:179-186. [ Publisher Site ][ PubMed ]

Miller, M.L., Aarde, S.M., Moreno, A.Y., Creehan, K.M., Janda, K.D. and Taffe, M.A Effects of active anti-methamphetamine vaccination on intravenous self-administration in rats. Drug Alcohol Depend, 2015, 153:29-36. [ Publisher Site ][ PubMed ]

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.

Aarde, S.M., Miller, M.L. Creehan, K.M., Vandewater, S.A. and Taffe, M.A. One day access to a running wheel reduces self-administration of d-methamphetamine, MDMA and Methylone. Drug Alcohol Depend, 2015, 151:151-158. [ Publisher Site ][ PubMed ]

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 ]

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.

Wright, M.J., Jr., Vandewater, S.A. and Taffe, M.A. Cannabidiol attenuates deficits of visuo-spatial associative memory induced by Δ9-tetrahydrocannabinol, Brit J Pharmacol, 2013, 170:1365-1373. [ PubMed ][ Publisher Link ] [Accompanying Commentary by Mechoulam and Parker, 2013, 170:1363-1364.]

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, M.J., Jr. and Taffe, M.A. Chronic periadolescent alcohol consumption produces presistent cognitive deficits in rhesus macaques, Neuropharmacology, 2014,  Jul 10. doi: 10.1016/j.neuropharm.2014.07.003. [Epub ahead of print][ PubMed ][ 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, Alcohol Clin Exp Res, 2013, Jun;37(6):952-960 [ PubMed ][ Publisher Link ]

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. Neurosci, 2013, 235:51-58 [ PubMed ][ Publisher Link ]

The Taffe Laboratory is supported by USPHS Grants R01 DA024705, R01 DA035281R01 DA035482 and R01 DA042211.

Previous work has been supported by USPHS grants  R01 DA024105, R01 AA016807, P20 DA024194, P60 AA006420, R01 DA18418, R21 AA013972, R01 DA13390, R01 MH61692 and P30 MH62261.