title: [Assessment of afobazole effects on diazepam withdrawal-induced anxiety in rats].
abstract: Long-term administration of benzodiazepines is known to be associated with drug dependence. The aim of the present work was to investigate the effects of non-benzodiazepine anxiolytic afobazole in the treatment of benzodiazepine withdrawal syndrome. Male outbred rats were treated with either diazepam (4.0 mg/kg, i.p.) or vehicle for 30 days and then abruptly withdrawn for 48 h. Animals were tested in the elevated plus maze test. In addition, neurochemical shifts were evaluated in the selected brain structures (striatum, hippocampus, hypothalamus, and frontal cortex) during diazepam withdrawal. Withdrawn animals made fewer entries and spent less time on the open arms than did vehicle-treated rats and demonstrated a decrease in the dopamine level in striatum as compared with vehicle and diazepam-treated ones. Afobazole (5.0 mg/kg, i.p.) effectively (i) ameliorated withdrawal-induced anxiety, returning behavioral pattern in the elevated plus maze test up to levels comparable to that in vehicle-treated animals, and (ii) increased withdrawal-reduced dopamine level (+23.8%, p < 0.05) in striatum. It is suggested that afobazole, due to its multitarget receptor action, can be useful in the diazepam withdrawal-induced anxiety blockade through modulation of dopaminergic system activity.
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects* / Q000494:pharmacology; D001008:Anxiety Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000494:pharmacology; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects; D003975:Diazepam / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009025:Morpholines / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology
chemical_list: C410924:2-((2-morpholino)ethylthio)-5-ethoxybenzimidazole; D014151:Anti-Anxiety Agents; D001562:Benzimidazoles; D009025:Morpholines; D003975:Diazepam