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Authors & Affiliations
Youyoung Lee, Wun-A Kook, Audrey Lynn Donio, Choon Gon Jang
Abstract
Adinazolam (ADZ) is one of the benzodiazepine-type new psychoactive substances (NPSs) with anxiolytic, anticonvulsant, and antidepressant effects. Although it is previously reported that high dose of ADZ administration impaired psychomotor performance and memory, abuse potential and drug dependence of ADZ have not been fully investigated. In this study, we evaluated whether ADZ has abuse potential, and lead in drug dependence and withdrawal symptoms when ADZ treatment was abruptly stopped. ADZ (0.01, 0.03, and 0.1 mg/kg/inf) increased intravenous self-administration in Sprague Dawley rats, suggesting the reinforcing effect of ADZ. Furthermore, the abstinence of ADZ after chronic administration of ADZ (3 and 6 mg/kg) caused several somatic withdrawal signs in C57BL/6J mice, including body tremor. Moreover, it also induced motivational withdrawal symptoms such as anxiety-relative behavior in elevated plus maze (EPM) test and memory deficit in Y-maze test. Also, ADZ administration significantly increased dopamine contents in thalamus, nucleus accumbens (NAc) and ventral tegmental area (VTA). Furthermore, ADZ administration caused maladaptation of dopaminergic system in the thalamus, NAc and VTA regions. Taken together, our results suggest that ADZ has abuse potential and can lead to drug dependence and withdrawal syndromes. (Supported by a grant 22214MFDS251 from Ministry of Food and Drug Safety)