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

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 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.

High ambient temperature facilitates the acquisition of 3,4-methylenedioxymethamphetamine (MDMA) self-administration

“…Changes in locomotion produced by the 5 mg/kg MDMA, i.v., condition were similar to the magnitude of changes produced by vapor inhalation or i.p. injection of METH, MDPV, or mephedrone [47–49, 69]. The magnitude of temperature reduction after this MDMA dose was also similar to the maximum effects observed for i.p.…”

Effective active vaccination against methamphetamine in female rats

“…Sealed exposure chambers were modified from the 259mm X 234mm X 209mm Allentown rat cage to regulate airflow and the delivery of vaporized drug to rats using e-cigarette type devices as has been previously described (Nguyen et al, 2016a; Nguyen et al, 2016b). A custom e-cigarette cartridge-triggering unit (Model SSV-1; La Jolla Alcohol Research, Inc; La Jolla CA) was controlled by MedPC IV software (MedAssociates, St Albans, VT) to deliver vapor puffs as scheduled.…”

Tolerance to hypothermic and antinoceptive effects of Δ9-tetrahydrocannabinol (THC) vapor inhalation in rats

“…A similar system results in hypothermia in mice following inhalation exposure to synthetic cannabinoid agonists (Lefever et al, 2017). Such systems also induces locomotor stimulation after inhalation of methamphetamine, mephedrone or 3,4-methylenedioxypyrovalerone (Nguyen, Aarde, Cole, Vandewater, Grant & Taffe, 2016) and can produce escalated self-administration of sufentanil to the point of dependence (Vendruscolo et al, 2017). Prior inhalation cannabinoid studies did not attempt to provide any evidence of plasticity of the cannabinoidtypical behavioral or physiological effects that attend repeated dosing.…”