Pharmacological effects of methamphetamine and alpha-PVP vapor and injection

Abstract

Vaporizing drugs in e-cigarettes is becoming a common method of administration for synthetic cathinones and classical stimulants. Heating during vaporization can expose the user to a cocktail of parent compound and thermolytic degradants, which could lead to different toxicological and pharmacological effects compared to ingesting the parent compound alone via injection or nasal inhalation. This study examined the in vivo toxicological and pharmacological effects of vaporized and injected methamphetamine (METH) and α-pyrrolidinopentiophenone (α-PVP). Male and female ICR mice were administered METH or α-PVP through vapor or i.p. injection. Dose-effect curves were determined for locomotor activity and a functional observational battery (FOB). METH and α-PVP vapor were also evaluated for place preference in male mice. Vapor exposure and injection led to more similarities than differences in toxicological and pharmacological effects. In the FOB, both routes of administration produced typical stimulant effects, and injection also increased some bizarre behaviors (e.g. licking, teeth chattering, darting). Both METH and α-PVP vapor exposure produced conditioned place preference. The two routes of administration had comparable efficacy in locomotor activation, with vapor producing longer lasting effects than injection. Females showed greater METH-induced locomotor activity, and greater incidence of a few somatic signs in the FOB than males. These results explore the toxicology of stimulant vapor inhalation in mice using an e-cigarette device. Despite the current technological and methodological difficulties, studying drug vapor promises to allow determination of toxicological effects of thermolytic products and flavor additives.

Analysis of neurotransmitter levels in addiction-related brain regions during synthetic cathinone self-administration in male Sprague-Dawley rats

“…In contrast, α-PVP contains a pyrrolidine ring, which produces DA and NE transporter blockade (Glennon and Young 2016;Marusich et al 2014). Despite a different mechanism of action, α-PVP and 4MMC produce typical stimulant effects including hyperactivity and stereotyped behavior (Marusich et al 2014;Marusich et al 2012;Marusich et al 2016). Importantly, α-PVP and 4MMC are readily self-administered by rats, indicating a propensity for addiction (Aarde et al 2015;Creehan et al 2015;Nguyen et al 2017a;Nguyen et al 2017b;Vandewater et al 2015).…”

Delivery of nicotine aerosol to mice via a modified electronic cigarette device

“…Results reported here serve as proof-of-principle for a novel device capable of translationally relevant delivery of nicotine aerosol for use in mechanistic studies of behavioral and biological effects of e-cigarettes. This apparatus has also been used to deliver aerosolized stimulants to rodents (Marusich et al, 2016). …”

Conditioned taste avoidance, conditioned place preference and hyperthermia induced by the second generation ‘bath salt’ α-pyrrolidinopentiophenone (α-PVP)

“…For example, Aarde and colleagues (2015) reported that in rats α-PVP was similar to MDPV in both potency and efficacy in supporting intravenous self-administration (see also Schindler et al, 2015). Additionally, Watterson et al (2014) demonstrated that in rats α-PVP dose-dependently decreased ICSS thresholds in a discrete trials current threshold procedure (Marusich et al, 2016). Consistent with this, Gatch et al (2015) reported that in mice α-PVP induced significant dose-dependent conditioned place preferences.…”