title: Intra-periaqueductal gray matter injections of midazolam fail to alter anxiety in plus-maze experienced mice.
abstract: It is well known that prior experience to the elevated plus-maze increases the avoidance of rodents to the open arms and impairs the anxiolytic-like effect of benzodiazepines evaluated during a subsequent exposure to the maze, a phenomenon known as "one-trial tolerance". Centrally injected benzodiazepine drugs attenuate anxiety in some limbic structures, such as hypothalamus, amygdala and the midbrain periaqueductal gray (PAG). This study investigated the effects of intra-PAG infusions of midazolam (MDZ) in maze-naïve and maze-experienced mice. The antiaversive effects of MDZ (3.0 nmol and 30 nmol in 0.1 microl) were evaluated by prior injection of flumazenil (16 nmol/0.1 microl), a benzodiazepine receptor antagonist, into the same midbrain site. Test videotapes were scored for conventional measures of anxiety and locomotor activity, as well as a range of ethological measures related to risk assessment. In maze-naïve mice, intra-PAG infusions of MDZ increased % open arm entries (3.0 nmol) and % open arm time (3.0 and 30 nmol). These effects were observed in the absence of significant changes in locomotor activity, indicating a selective anxiolytic-like effect of MDZ. The antiaversive effects of MDZ were completely blocked by prior injection of flumazenil which in turn did not alter any other behavioral measure. In maze-experienced mice, intra-PAG infusion of MDZ did not modify any behavioral measure. Taken together, present results corroborate previous studies demonstrating that GABA/benzodiazepine receptor complex located within the PAG plays a role on anxiety modulation in maze-naïve mice as well as indicate its involvement in the OTT phenomenon.
authors.affiliation: Grupo de Psicobiologia/Depto de Psicologia/CECH-UFSCar, Rod. Washington Luís Km 235, São Carlos, SP, Brazil.
authors.forename: Luciana Maria
authors.initials: LM
authors.lastname: dos Reis
authors.forename: Azair
authors.initials: A
authors.lastname: Canto-de-Souza
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D005239:Fear / Q000187:drug effects / Q000502:physiology; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008874:Midazolam / Q000494:pharmacology* / Q000627:therapeutic use; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000502:physiology; D011963:Receptors, GABA-A / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D018757:GABA Modulators; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D008874:Midazolam