title: Blockade of fear-induced antinociception with intra-amygdala infusion of midazolam: Influence of prior test experience.
abstract: Intra-amygdala infusion of midazolam, a benzodiazepine receptor agonist, produces anxiolytic-like effects in mice when first exposed to the elevated plus-maze (EPM) and blocks antinociception induced in mice confined in the open arm of the EPM. However, benzodiazepines fail to alter anxiety in maze-experienced rodents, a phenomenon defined as "one-trial tolerance" (OTT). The main purpose of the present study was to investigate whether intra-amygdala midazolam attenuates the open arm-induced antinociception (OAA) in maze-experienced mice. Nociception was assessed by the writhing test (intra-peritoneal injection of 0.6% acetic acid). In Experiment 1, nociception was recorded in maze-experienced mice without prior drug treatment. Experiment 2 investigated the effects of systemic midazolam (0.5, 1.0 and 2.0 mg/kg, s.c.), injected before EPM trial 2, on OAA in maze-experienced mice. In Experiment 3, the effects on OAA of intra-amygdala midazolam (30 nmol/0.1 microl), injected before trial 1 (maze-naive) or before trial 2 (maze-experienced), were observed. The effects on OAA of intra-amygdala midazolam injected before trial 1 and trial 2 were also investigated (Experiment 4). The results showed that OAA remained unchanged in maze-experienced mice and was insensitive to systemic midazolam. However, intra-amygdala midazolam attenuated OAA in maze-naive mice, but not in maze-experienced mice. Even when given before both trial 1 and trial 2, intra-amygdala midazolam failed to alter OAA in maze-experienced mice. Taken together, these results confirm that the GABA(A)/benzodiazepine receptor complex located within the amygdala plays a role in OAA in maze-naive mice. The lack of effects following systemic or intra-amygdala midazolam on OAA in maze-experienced mice suggests that the OTT is also observed in the modulation of nociception and that the GABA(A)/benzodiazepine receptor located within this limbic forebrain structure participates in this process.
authors.affiliation: Grupo de Psicobiologia/Depto de Psicologia/CECH-UFSCar, Rod. Washington Luís, Km 235, 13565-905 São Carlos, SP, Brazil.
authors.forename: Daniela
authors.initials: D
authors.lastname: Baptista
authors.forename: Karina
authors.initials: K
authors.lastname: Bussadori
authors.forename: Ricardo Luiz
authors.initials: RL
authors.lastname: Nunes-de-Souza
authors.forename: Azair
authors.initials: A
authors.lastname: Canto-de-Souza
mesh_terms: D019342:Acetic Acid; D000679:Amygdala / Q000187:drug effects* / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002404:Catheterization; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects* / Q000502:physiology / Q000523:psychology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008845:Microinjections; D008874:Midazolam / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D010147:Pain Measurement; D013997:Time Factors
chemical_list: D014151:Anti-Anxiety Agents; D019342:Acetic Acid; D008874:Midazolam