title: A new exposure model to evaluate smoked illicit drugs in rodents: A study of crack cocaine.
abstract: The use of smoked illicit drugs has spread dramatically, but few studies use proper devices to expose animals to inhalational abused drugs despite the availability of numerous smoking devices that mimic tobacco exposure in rodents. Therefore, the present study developed an inexpensive device to easily expose laboratory animals to smoked drugs. We used crack cocaine as the drug of abuse, and the cocaine plasma levels and the behaviors of animals intoxicated with the crack cocaine were evaluated to prove inhaled drug absorption and systemic activity. We developed an acrylic device with two chambers that were interconnected and separated by a hatch. Three doses of crack (100, 250, or 500 mg), which contained 63.7% cocaine, were burned in a pipe, and the rats were exposed to the smoke for 5 or 10 min (n=5/amount/period). Exposure to the 250-mg dose for 10 min achieved cocaine plasma levels that were similar to those of users (170 ng/mL). Behavioral evaluations were also performed to validate the methodology. Rats (n=10/group) for these evaluations were exposed to 250 mg of crack cocaine or air for 10 min, twice daily, for 28 consecutive days. Open-field evaluations were performed at three different periods throughout the experimental design. Exposed animals exhibited transient anorexia, increased motor activity, and shorter stays in central areas of the open field, which suggests reduced anxiety. Therefore, the developed model effectively exposed animals to crack cocaine, and this model may be useful for the investigation of other inhalational abused drugs.
authors.affiliation: Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo (ICAQF-UNIFESP), Diadema, S.P., Brazil; Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, S.P., Brazil. Electronic address: imhueza@unifesp.br.
authors.forename: Isis M
authors.initials: IM
authors.lastname: Hueza
authors.affiliation: Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, S.P., Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: Ponce
authors.affiliation: Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo (ICAQF-UNIFESP), Diadema, S.P., Brazil; Department of Clinical Chemistry and Toxicology, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, S.P., Brazil.
authors.forename: Raphael C T
authors.initials: RC
authors.lastname: Garcia
authors.affiliation: Department of Clinical Chemistry and Toxicology, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, S.P., Brazil.
authors.forename: Tânia
authors.initials: T
authors.lastname: Marcourakis
authors.affiliation: Department of Clinical Chemistry and Toxicology, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, S.P., Brazil.
authors.forename: Maurício
authors.initials: M
authors.lastname: Yonamine
authors.affiliation: Department of Clinical Chemistry and Toxicology, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, S.P., Brazil.
authors.forename: Cínthia de C
authors.initials: Cde C
authors.lastname: Mantovani
authors.affiliation: Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, S.P., Brazil.
authors.forename: Thiago B
authors.initials: TB
authors.lastname: Kirsten
mesh_terms: D000818:Animals; D016578:Crack Cocaine / Q000009:adverse effects*; D013287:Illicit Drugs / Q000009:adverse effects*; D008297:Male; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D012906:Smoke / Q000009:adverse effects*; D019966:Substance-Related Disorders / Q000209:etiology*; D014026:Nicotiana
chemical_list: D016578:Crack Cocaine; D013287:Illicit Drugs; D012906:Smoke
keywords: Drug of abuse; Exposure device; Freebase cocaine; Pulmonary route