Papel dos receptores GABA-benzodiazpínicos da amigdala na modulação da ansiedade em camundongos ingênuos e reexpostos ao labirinto em cruz elevado
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2007-12-17Autor
Barbalho, Cilene Aparecida
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Previous studies demonstrated that microinjections of midazolam (MDZ), GABAAbenzodiazepine
(BDZs) receptor agonist, into the amygdala (AMY) produce anxiolytic effects
in the elevated plus-maze (EPM) naïve-mice. During the reexposured to the EPM is
increasing avoidance of open arms and impairs the anxiolytic like effect of BDZs,
phenomenon characterized as "one trial tolerance" (OTT). This study investigated the effects
of intra-AMY infusions of midazolam (MDZ) in EPM-experienced mice and GABAA-BDZs
receptor antagonist, flumazenil (FMZ), intra-AMY, on anxiety in EPM-naïve and EPMexperienced
mice. The analysis was performed on conventional measures of anxiety (% open
arm entries and % open arm time), locomotor activity (frequency of closed arm entries) and a
range of ethological measures related to risk assessment. The intra-AMY infusions of MDZ
(3.0 and 30 nmol/0.1µl) increased % open arm entries (%OA) and % open arm time (%OT) in
EPM-experienced mice. The analysis of ethological measures demonstrated that MDZ
increased the total head dipping (THD) and decreased percent protected head dipping
(%PHD) and percent protected stretched attend postures (%PSAP) without any significant
change to total stretched attend (TSAP), total rearing (TR) and total immobility (TI). The
intra-AMY infusions of FMZ 16 (nmol/0.1µl), increased %OA and %OT in maze-naïve and
maze-experienced mice. The analysis of ethological measures reveals that FMZ increased the
THD and TSAP and decreased %PHD and %PSAP without any significant change to TSAP,
TR and TI in maze-naïve. In EPM-experienced mice, intra-AMY infusions of FMZ only
increased TSAP without alter any other ethological measure. Interestingly, combined
administration of DMCM (1.0 mg/Kg) and FMZ (2.0 nmol) significantly decreased the %OA
and %OT when compared to vehicle+vehicle. The anxiogenic-like effect produced by
GABAA receptor inverse agonist was blocked by intra-AMY infusions of FMZ. FMZ plus
vehicle produced absence of effects. These effects were observed in the absence of significant changes in locomotor activity, indicating a selective anxiolytic-like effect for MDZ and FMZ.
Interestingly, both benzodiazepine receptor agonist and antagonist, MDZ and FLU,
respectively, produced selective anxiolytic-like effects when injected into the amygdala in
maze-experienced mice. Together, present results demonstrate that GABA-benzodiazepine
receptor complex located within the AMY did not involvement in the OTT phenomenon.
However, the anxiogenic-like effect produced by GABA-BDZs receptor inverse agonist was
blocked by intra-AMY infusions of FMZ. These results suggest that the emotional state
induced by plus-maze test someway releases endogenous benzodiazepine receptor inverse
agonist within the amygdala.