Exposure of rats to the open elevated plus maze induces antinociception during the first phase of the formalin test.
Open elevated plus maze; Fear-induced antinociception; Formalin test; Fear; Stress.
Animals exposed to threatening environments exhibit defensive behaviors, including fear induced antinociception. The open elevated plus maze (OEM) with the formalin test has proven relevant to understanding the mechanisms underlying this type of antinociception. Although studies have investigated this response during the second phase of the formalin test, data on the first phase are scarce. In this context, the objective of this research was to investigate the effect of exposing rats to the OEM during the first phase of the formalin test, as well as to evaluate the influence of repeated exposures to the OEM on nociception. Adult Wistar rats were used, distributed into two experiments. In Experiment I, the animals received an injection of formalin (2.5%, 50 µL) in the right hind limb and were exposed to three distinct environments: glass box (control), closed elevated plus maze (CPM), or open elevated plus maze (OPM), to record licking time during the first phase of the test. In these same animals, nociceptive responses during the second phase of the test were evaluated in the glass box. In Experiment II, animals were exposed one, two, three, four, or six times to CPM or OPM (2.5% formalin, 50 µL, was injected only on the last day of exposure) to record licking time on the right hind limb. The results of Experiment I revealed significant differences in licking time between the control and LCEa groups, and between the LCEf and LCEa groups, indicating that exposure to LCEa during the first phase of the formalin test induces antinociception, which is rapidly attenuated after removal of the aversive environment. In Experiment II, antinociception was observed to be maintained in inexperienced animals and in animals repeatedly exposed to LCEa for up to six exposures. Thus, it can be inferred that LCEa-induced antinociception occurs during the first phase of the formalin test and that this response is likely mediated by non-opioid mechanisms, since repeated exposures did not promote antinociceptive tolerance.