title: Abuse potential and dopaminergic effect of alkyl nitrites.
abstract: The abuse of alkyl nitrites is common among adolescents and young adults worldwide. However, the information regarding the effects of alkyl nitrites on the central nervous system and the associated psychological abuse potential is scarce. The abuse potential of 3 representative alkyl nitrites - isobutyl nitrite, isoamyl nitrite, and butyl nitrite - was evaluated in mice using conditioned place preference tests with an unbiased method. The dopamine levels released by synaptosomes extracted from the striatal region were measured using high performance liquid chromatography. Mice treated with the test substances (50mg/kg, i.p.) exhibited a significantly increased drug-paired place preference. Moreover, greater levels of dopamine were released by striatal region synaptosomes in response to isobutyl nitrite treatment in mice. Thus, our findings suggest that alkyl nitrites could lead to psychological dependence and dopaminergic effects. Furthermore, these results provide scientific evidence to support the regulation of alkyl nitrites as psychoactive substances in the future.
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, 187 Osong Saengmyeong 2-ro, Heungdeok-gu, Chungju-shi 28159, Republic of Korea.
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Jeon
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, 187 Osong Saengmyeong 2-ro, Heungdeok-gu, Chungju-shi 28159, Republic of Korea.
authors.forename: Yun Ji
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, 187 Osong Saengmyeong 2-ro, Heungdeok-gu, Chungju-shi 28159, Republic of Korea.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, 187 Osong Saengmyeong 2-ro, Heungdeok-gu, Chungju-shi 28159, Republic of Korea.
authors.forename: Jisoon
authors.initials: J
authors.lastname: Shin
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, 187 Osong Saengmyeong 2-ro, Heungdeok-gu, Chungju-shi 28159, Republic of Korea.
authors.forename: Jaesuk
authors.initials: J
authors.lastname: Yun
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, 187 Osong Saengmyeong 2-ro, Heungdeok-gu, Chungju-shi 28159, Republic of Korea.
authors.forename: Kyoungmoon
authors.initials: K
authors.lastname: Han
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, 187 Osong Saengmyeong 2-ro, Heungdeok-gu, Chungju-shi 28159, Republic of Korea.
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Park
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, 187 Osong Saengmyeong 2-ro, Heungdeok-gu, Chungju-shi 28159, Republic of Korea.
authors.forename: Hyung Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, 187 Osong Saengmyeong 2-ro, Heungdeok-gu, Chungju-shi 28159, Republic of Korea. Electronic address: chahj1@korea.kr.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Cha
mesh_terms: D000680:Amyl Nitrite / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009573:Nitrites / Q000737:chemistry / Q000633:toxicity*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D019966:Substance-Related Disorders / Q000209:etiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D000680:Amyl Nitrite; D004298:Dopamine; D009573:Nitrites; D016194:Receptors, N-Methyl-D-Aspartate; C024225:n-butyl nitrite; C048958:isoamyl nitrite; C018086:isobutyl nitrite
keywords: Butyl nitrite; Conditioned place preference; Dependence; Dopamine; HPLC; Isoamyl nitrite; Isobutyl nitrite; Synaptosome