Opioidergic and nitrergic systems mediate the anticonvulsant effect of mefloquine and chloroquine on seizures induced by pentylenetetrazol and maximal electroshock in mice

Abstract

Studies have previously demonstrated a relationship between social status and anxiety disorders such as panic disorder. Repeated episodes of panic attacks do not occur in combination with an actual fear stimulus or stressor. However, social ranking modulates the perception of the social signals of a threat or stressor. The hypothalamic nuclei are well‑known for their role in the elaboration of fear‑induced reactions. The dorsomedial hypothalamus (DMH) and the ventromedial hypothalamic (VMH) nuclei are hypothalamic subnuclei involved in the processing of threatening stimuli‑evoked aversive response and innate fear development. These structures are also located in the medial amygdala‑hypothalamus‑brainstem circuit that modulates innate fear‑induced defensive behaviors. This work aimed to investigate the relationship between social hierarchy and innate fear‑induced panic‑like responses in male rats. In our study, the dominance tube test was used to determine the social hierarchy. Then, DMH/VMH nuclei were unilaterally implanted with a guide cannula. After intra‑DMH/VMH injection of bicuculline (GABAA receptor antagonist), both innate fear induction and differences in dominant/subordinate rats were evaluated by the open field test. Intra‑DMH/VMH bicuculline increased the frequency of defensive immobility, forward escape movements, and crossing behaviors, as well as the duration of defensive immobility and forward escape movements in dominant rats. Subordinate rats showed a higher frequency of defensive attention, defensive immobility, and crossing than dominant rats. Additionally, dominant rats demonstrated a lower duration of defensive attention and defensive immobility than subordinate rats. Dominant rats seemed to adopt a form of innate‑fear characterized by increased proactivity with the environment. In contrast, subordinate rats exhibited a reactive form of innate‑fear characterized by passivity and freezing.