Original Article

Neuropsychopharmacology (2016) 41, 2759–2771; doi:10.1038/npp.2016.88; published online 29 June 2016

Locomotor Stimulant and Rewarding Effects of Inhaling Methamphetamine, MDPV, and Mephedrone via Electronic Cigarette-Type Technology

Jacques D Nguyen1, Shawn M Aarde1, Maury Cole2, Sophia A Vandewater1, Yanabel Grant1 and Michael A Taffe1

  1. 1Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA
  2. 2La Jolla Alcohol Research, La Jolla, CA, USA

Correspondence: Dr MA Taffe, Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, SP30-2400, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Tel: +1 858 784 7228, Fax: +1 858 784 7405, E-mail: mtaffe@scripps.edu

Received 19 April 2016; Revised 2 June 2016; Accepted 3 June 2016
Accepted article preview online 9 June 2016; Advance online publication 29 June 2016

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Abstract

Although inhaled exposure to drugs is a prevalent route of administration for human substance abusers, preclinical models that incorporate inhaled exposure to psychomotor stimulants are not commonly available. Using a novel method that incorporates electronic cigarette-type technology to facilitate inhalation, male Wistar rats were exposed to vaporized methamphetamine (MA), 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone (4-methylmethcathinone) in propylene glycol vehicle using concentrations ranging from 12.5 to 200mg/ml. Rats exhibited increases in spontaneous locomotor activity, measured by implanted radiotelemetry, following exposure to methamphetamine (12.5 and 100mg/ml), MDPV (25, 50, and 100mg/ml), and mephedrone (200mg/ml). Locomotor effects were blocked by pretreatment with the dopamine D1-like receptor antagonist SCH23390 (10μg/kg, intraperitoneal (i.p.)). MA and MDPV vapor inhalation also altered activity on a running wheel in a biphasic manner. An additional group of rats was trained on a discrete trial intracranial self-stimulation (ICSS) procedure interpreted to assess brain reward status. ICSS-trained rats that received vaporized MA, MDPV, or mephedrone exhibited a significant reduction in threshold of ICSS reward compared with vehicle. The effect of vapor inhalation of the stimulants was found comparable to the locomotor and ICSS threshold-reducing effects of i.p. injection of mephedrone (5.0mg/kg), MA (0.5–1.0mg/kg), or MDPV (0.5–1.0mg/kg). These data provide robust validation of e-cigarette-type technology as a model for inhaled delivery of vaporized psychostimulants. Finally, these studies demonstrate the potential for human use of e-cigarettes to facilitate covert use of a range of psychoactive stimulants. Thus, these devices pose health risks beyond their intended application for the delivery of nicotine.

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