A new exposure model to evaluate smoked illicit drugs in rodents: A study of crack cocaine

Hueza, Isis Machado; Ponce, Fernando; Garcia, Raphael Caio Tamborelli; Marcourakis, Tânia; Yonamine, Maurı́cio; Mantovani, Cinthia de Carvalho; Kirsten, Thiago Berti

doi:10.1016/j.vascn.2015.09.003

Cited by 9 publications

(5 citation statements)

References 32 publications

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“…The system was configured at 7W using a 1.8Ω atomizer. During exposure periods, approximately 0.01 mL of liquid was vaporized, and the chamber was filled with drug vapor over the course of 10 s. The mouse then remained in the exposure chamber for 5 min (Hueza et al, 2016; Meng et al, 1997, 1999), with no additional vapor introduced.…”

Section: 0 Methodsmentioning

confidence: 99%

Pharmacological effects of methamphetamine and alpha-PVP vapor and injection

et al. 2016

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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.

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Section: 0 Methodsmentioning

confidence: 99%

Pharmacological effects of methamphetamine and alpha-PVP vapor and injection

et al. 2016

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“…Monkeys can be trained to smoke cocaine base (Comer et al, 1994(Comer et al, , 1995 or methamphetamine (Newman and Carroll, 2006) and rats and mice have been exposed involuntarily to cocaine or methamphetamine in a restraint preparation (Lichtman et al, 1995;Meng et al, 1999). Apart from one recently described model for crack cocaine (Hueza et al, 2016), preclinical models of inhaled exposure to stimulants in unrestrained are not generally available.…”

Section: Introductionmentioning

confidence: 99%

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

Nguyen

Aarde

Cole

et al. 2016

Neuropsychopharmacol

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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.

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“…The exposure apparatus, developed by Hueza et al, 10 consists of two chambers interconnected and separated by a hatch. Briefly, the animals are placed in an entrance chamber before the exposure and then transferred to the exposure chamber, where the smoke of 250 mg of burned crack cocaine is sucked in.…”

Section: The Apparatus and Crack Exposurementioning

confidence: 99%

“…The exposure was performed daily, twice a day with an interval of 12 h, for 10 min each. The drug here employed was the same used by Hueza et al, 10 thus, a single exposure of 250 mg of crack smoke for 10 min promotes serum levels of cocaine around 170 ng/mL. During the experimental period, the pregnant rats were observed daily in relation to clinical signs, food waste, morbidity, and mortality.…”

Section: Animal Exposurementioning

confidence: 99%

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Crack cocaine smoke on pregnant rats: Maternal evaluation and teratogenic effect

et al. 2019

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This study aimed to evaluate maternal toxicity, teratogenic, and placental oxidative effects resulting from the exposure of rats to crack cocaine smoke during pregnancy. Pregnant rats were exposed either to the smoke of crack and ashes (Crack) or to the smoke of ashes alone, nonexposed or pair-fed with the Crack group. Crack group was exposed to the smoke resulting from the burning of 250 mg of crack for 10 min, twice a day, from 7 days prior to mating until cesarian on gestational day 20. Placental oxidative stress and classical parameters of maternal and fetal evaluation were studied, in addition to the morphometric analysis of the fetal metamers. Even in the absence of changes in body weight gain and feed intake, crack altered the reproductive performance of dams. Exposure to the drug promoted late closure of the fetal fontanel. Furthermore, the morphometric study of the brain mass (BM)/skull cap ratio revealed a decrease in the BM of the fetuses exposed to the drug. Exposure to crack has an oxidative potential in fetal development, since exposure to the drug promoted placental lipid peroxidation. Our study showed that daily exposure to crack, even in lower frequency than that performed by users, has a teratogenic potential.

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A new exposure model to evaluate smoked illicit drugs in rodents: A study of crack cocaine

Cited by 9 publications

References 32 publications

Pharmacological effects of methamphetamine and alpha-PVP vapor and injection

Pharmacological effects of methamphetamine and alpha-PVP vapor and injection

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

Crack cocaine smoke on pregnant rats: Maternal evaluation and teratogenic effect

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