title: Enhanced dorsolateral periaqueductal gray activity counteracts the anxiolytic response to midazolam on the elevated plus-maze Trial 2 in rats.
abstract: Rodents previously (Trial 1) experienced in the elevated plus-maze (EPM) apparatus no longer respond to anxiolytic-like drugs during retesting (Trial 2). In view of the fact that the dorsolateral periaqueductal gray (dlPAG) modulates fear/anxiety-like behavior, the present study sought to determine its role in this phenomenon. In order to address this issue, EPM-experienced rats that had received lidocaine, a drug which produces a reversible functional deactivation, intra-dlPAG pre-Trial 1, post-Trial 1 or pre-Trial 2, were systemically injected with the benzodiazepine midazolam and submitted to the EPM apparatus. According to the results, 0.25 mg/kg midazolam increased open arms exploration and reduced risk assessment behavior, suggesting an anxiolytic-like effect in EPM-naive rats, regardless of the intra-dlPAG treatment. EPM-experienced rats administered with midazolam only displayed a similar pattern of behavior when lidocaine was administered intra-dlPAG pre-Trial 2, but not pre- or post-Trial 1. These effects were observed in the absence of changes in enclosed arms entries, an EPM general exploratory activity index. The present results suggest that an increased activity of the dlPAG during Trial 2 would explain the lack of anxiolytic-like effect of drugs elicited by prior EPM test experience.
authors.affiliation: Departamento de Farmacologia, FMRP-USP, Av. Bandeirantes, 3900, Ribeirão Preto, SP 14049-900, Brazil.
authors.forename: Leandro José
authors.initials: LJ
authors.lastname: Bertoglio
authors.forename: Cláudia
authors.initials: C
authors.lastname: Anzini
authors.forename: Cilene
authors.initials: C
authors.lastname: Lino-de-Oliveira
authors.forename: Antônio Pádua
authors.initials: AP
authors.lastname: Carobrez
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects*; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004347:Drug Interactions; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008874:Midazolam / Q000008:administration & dosage*; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000779:Anesthetics, Local; D014151:Anti-Anxiety Agents; D008012:Lidocaine; D008874:Midazolam