MICROINJECTION OF MIDAZOLAM IN POSTERIOR HYPOTHALAMUS DOES NOT REVERT INDUCED ANTINOCICEPTION IN THE OPEN HIGH CROSS MAZE IN RATS FEMALES
Fear-induced antinociception. Elevated plus maze. Formalin test.
Animals exposure to threatening situations (innate or learned nature) induces a set of species-specific defense behaviors, among them, antinociception. It has been shown that rodents exposed to the elevated plus maze (four open arms, oEPM), an aversive situation, exhibit high magnitude antinociception. However, the mechanisms involved in such antinociception have not yet been elucidated. The present study investigated if antinociception induced in female rats exposed to oEPM could be reversed by microinjection of midazolam into the posterior hypothalamus. Thus, female rats received a right unilateral cannula implant in the posterior hypothalamus. One to three days after the implantation of the cannula, the animals were manipulated and
habituated to the experimental room for three days. On the day of the test, animals were submitted to the formalin test (2.5%, 0.05 mL) injected subcutaneously into the right hind paw and then the first test phase (5 minutes initial) was recorded in a glass vat. Fifteen minutes after formalin injection, the animals received microinjection of saline 0,9% or midazolam (5 nmoles) into the posterior hypothalamus. And, twenty-five
minutes after the formalin injection, the animals were individually exposed to the closed or open EPM for recording the lick time on the foot for 10 minutes (Phase 2: 25-35 minutes). During the second phase of the formalin test, the experiment was recorded through a computer-camera circuit for further behavior analysis and nociceptive response analysis. The results show that the female rats exhibited elevated plus maze antinociception, but this response was not reversed by microinjection of midazolam (5 nmoles) in the posterior hypothalamus. However, for a more robust conclusion about the involvement of the posterior hypothalamus in the oEPM-induced antinociception, additional studies are required at different doses since the literature indicates that larger doses appear to have an effect on the posterior hypothalamus in animal models of fear- induced antinociception.