title: The benzodiazepine midazolam acts on the expression of the defensive behavior, but not on the processing of aversive information, produced by exposure to the elevated plus maze and electrical stimulations applied to the inferior colliculus of rats.
abstract: Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses such as freezing and escape behavior. Freezing also results after termination of this stimulation (post-stimulation freezing; PSF). Whereas these responses are critically mediated by GABA in the dPAG, it is unclear how GABA-benzodiazepine mechanisms mediate the expression of fear (freezing and escape behaviors) and the processing of aversive information (PSF) produced by electrical stimulation of the IC. Since dorsal (ICd) and ventral regions (ICv) of the IC react differentially to aversive stimulation, we hypothesized that these regions might be sensitive to the action of benzodiazepine drugs when rats are submitted to animal models of anxiety: the elevated plus maze (EPM) and the IC electrical stimulation procedure. Midazolam (5, 10 or 20 nmol) was injected into the ICd or ICv of rats subjected to one of these tests. Intra-ICv, but not intra-ICd injections, of midazolam reduced the aversiveness of the IC electrical stimulation and decreased fear in the EPM, as assessed by its traditional and complementary measures. In contrast, the IC post-stimulation freezing remained unaltered with midazolam treatments. Thus, there is a clear pharmacological dissociation in the reactivity of dorsal and ventral regions of the IC to fear-provoking stimuli of the two animal models of anxiety used in this study. The present results support the proposal that benzodiazepine-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the IC.
authors.affiliation: Laboratory of Neuropsychopharmacology, FFCLRP, Universidade de São Paulo, Campus USP, Ribeirão Preto, SP 14040-901, Brazil; Instituto de Neurociências e Comportamento, Avenida do Café, 2450, Ribeirão Preto, SP 14050-000, Brazil. Electronic address: mitsuko@usp.br.
authors.forename: Viviane M
authors.initials: VM
authors.lastname: Saito
authors.affiliation: Laboratory of Neuropsychopharmacology, FFCLRP, Universidade de São Paulo, Campus USP, Ribeirão Preto, SP 14040-901, Brazil; Instituto de Neurociências e Comportamento, Avenida do Café, 2450, Ribeirão Preto, SP 14050-000, Brazil.
authors.forename: Marcus L
authors.initials: ML
authors.lastname: Brandão
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004924:Escape Reaction / Q000187:drug effects* / Q000502:physiology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000187:drug effects / Q000502:physiology; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects* / Q000502:physiology; D018757:GABA Modulators / Q000494:pharmacology; D007245:Inferior Colliculi / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D011897:Random Allocation; D017208:Rats, Wistar
chemical_list: D014151:Anti-Anxiety Agents; D018757:GABA Modulators; D008874:Midazolam
keywords: Anxiety; Benzodiazepine; Electrical stimulation; Fear; Inferior colliculus; Midazolam