Journal Article

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

Nguyen, Jacques D, Vandewater, Sophia A, Grant, Yanabel, Taffe, Michael A, Aarde, Shawn M, Cole, Maury

2016

Overview

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 200 mg/ml. Rats exhibited increases in spontaneous locomotor activity, measured by implanted radiotelemetry, following exposure to methamphetamine (12.5 and 100 mg/ml), MDPV (25, 50, and 100 mg/ml), and mephedrone (200 mg/ml). Locomotor effects were blocked by pretreatment with the dopamine D1-like receptor antagonist SCH23390 (10 μg/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 (5.0 mg/kg), MA (0.5-1.0 mg/kg), or MDPV (0.5-1.0 mg/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.

• Publisher: Nature Publishing Group
• Subject: Administration, Inhalation / Animals / Behavior / Benzazepines - administration & dosage / Benzazepines - pharmacology / Benzodioxoles - administration & dosage / Benzodioxoles - pharmacology / Body temperature / Central Nervous System Stimulants - administration & dosage / Central Nervous System Stimulants - pharmacology / Cocaine / Conditioning, Operant / Dopamine Antagonists - administration & dosage / Dopamine Antagonists - pharmacology / Dose-Response Relationship, Drug / Drugs / Electronic cigarettes / Electronic Nicotine Delivery Systems / Laboratory animals / Locomotion - drug effects / Male / Methamphetamine / Methamphetamine - administration & dosage / Methamphetamine - analogs & derivatives / Methamphetamine - pharmacology / Neurobiology / Neurosciences / Original / Pyrrolidines - administration & dosage / Pyrrolidines - pharmacology / Rats / Rats, Wistar / Research centers / Reward / Self Administration / Stimulants / Telemetry