title: 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.
authors.affiliation: Center for Drug Discovery, RTI International, 3040 Cornwallis Rd., Research Triangle Park, NC 27709, USA. Electronic address: jmarusich@rti.org.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Marusich
authors.affiliation: Center for Drug Discovery, RTI International, 3040 Cornwallis Rd., Research Triangle Park, NC 27709, USA.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Lefever
authors.affiliation: Center for Drug Discovery, RTI International, 3040 Cornwallis Rd., Research Triangle Park, NC 27709, USA.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Blough
authors.affiliation: Center for Drug Discovery, RTI International, 3040 Cornwallis Rd., Research Triangle Park, NC 27709, USA.
authors.forename: Brian F
authors.initials: BF
authors.lastname: Thomas
authors.affiliation: Center for Drug Discovery, RTI International, 3040 Cornwallis Rd., Research Triangle Park, NC 27709, USA.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Wiley
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D016503:Drug Delivery Systems; D005260:Female; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D051379:Mice; D008813:Mice, Inbred ICR; D010422:Pentanones / Q000008:administration & dosage*; D011759:Pyrrolidines / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D000697:Central Nervous System Stimulants; D010422:Pentanones; D011759:Pyrrolidines; D008694:Methamphetamine; C000592273:1-phenyl-2-(1-pyrrolidinyl)-1-pentanone
keywords: Conditioned place preference; Functional observational battery; Locomotor activity; Methamphetamine; Vapor; α-PVP