title: Neurotoxicity induced by alkyl nitrites: Impairment in learning/memory and motor coordination.
abstract: Although alkyl nitrites are used as recreational drugs, there is only little research data regarding their effects on the central nervous system including their neurotoxicity. This study investigated the neurotoxicity of three representative alkyl nitrites (isobutyl nitrite, isoamyl nitrite, and butyl nitrite), and whether it affected learning/memory function and motor coordination in rodents. Morris water maze test was performed in mice after administrating the mice with varying doses of the substances in two different injection schedules of memory acquisition and memory retention. A rota-rod test was then performed in rats. All tested alkyl nitrites lowered the rodents' capacity for learning and memory, as assessed by both the acquisition and retention tests. The results of the rota-rod test showed that isobutyl nitrite in particular impaired motor coordination in chronically treated rats. The mice chronically injected with isoamyl nitrite also showed impaired function, while butyl nitrite had no significant effect. The results of the water maze test suggest that alkyl nitrites may impair learning and memory. Additionally, isoamyl nitrite affected the rodents' motor coordination ability. Collectively, our findings suggest that alkyl nitrites may induce neurotoxicity, especially on the aspect of learning and memory function.
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
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: 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: 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
mesh_terms: D000680:Amyl Nitrite / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D001259:Ataxia / Q000139:chemically induced / Q000523:psychology*; D007858:Learning / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009573:Nitrites / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D045442:Rotarod Performance Test; D065853:Spatial Learning / Q000187:drug effects
chemical_list: D009573:Nitrites; C024225:n-butyl nitrite; C048958:isoamyl nitrite; D000680:Amyl Nitrite; C018086:isobutyl nitrite
keywords: Alkyl nitrites; Learning and memory; Motor coordination; Neurotoxicity; Rota-rod; Water maze