Papel dos receptores GABA-benzodiazepínicos da matéria cinzenta periaquedutal na modulação da ansiedade em camundongos ingênuos e reexpostos ao labirinto em cruz elevado
Resumo
It is well known that the previous experience to the elevated plus-maze (EPM)
increases the avoidance of rodents to the open arms and impairs the anxiolytic-like effect of
benzodiazepines in a subsequent exposure to the EPM, a phenomenon known as "one trial
tolerance" (OTT). This study investigated the effects of intra-periaqueductal gray matter
(PAG) infusions of midazolam (MDZ) in EPM-naïve and EPM-experienced mice. The
antiaversive effects of MDZ were also evaluated after prior injection of flumazenil, a
benzodiazepine receptor antagonist, into to same midbrain site. Test videotapes were scored
for conventional measures of anxiety (% open arm entries and % open arm time) and
locomotor activity (frequency of closed arm entries), as well as a range of ethological
measures related to risk assessment (e.g. stretch attend postures; head dips, etc). In EPMnaïve
mice, intra-PAG infusions of MDZ increased % open arm entries (2.26 nmol) and %
open arm time (2.26 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 (16
nmol) into the same midbrain site, and did not alter any behavioral measures per se. In EPMexperienced
mice, intra-PAG infusion of MDZ did not modify any behavioral measures.
Taken together, present results demonstrates that GABA-benzodiazepine receptor complex
located within the PAG plays a role on anxiety modulation in EPM-naïve mice as well as
indicates its involvement in the OTT phenomenon.