NEUROANATOMICAL CHARACTERIZATION OF FOS INDUCTION IN RAT BEHAVIORAL-MODELS OF ANXIETY

Immunohistochemical staining for Fos-like immunoreactivity (Fos-LI) wa s used to map functional activation in discrete brain regions of rats processed in three empirical models of anxiety: foot shock avoidance r esponding in a shuttle box, the elevated plus maze, and an air puff-in duced ultrasonic vocalization test. The avoidance test and elevated pl us maze induced prominent Fos-LI in select brain regions, including th e medial prefrontal, cingulate, and ventrolateral orbital cortices, ta enia tecta, nucleus accumbens, paraventricular nucleus of the hypothal amus, medial nucleus of the amygdala and lateral septum. Air puff stim uli that produced ultrasonic vocalizations induced Fos-LI to a more li mited extent compared to the plus maze and avoidance test, with only t he medial prefrontal cortex, medial nucleus of the amygdala, and later al septum being significantly affected by air-puff. Even though the se nsory stimuli and environmental conditions associated with the three a nxiety models were markedly different, specific common forebrain regio ns were affected, i.e. the medial prefrontal cortex, medial amygdala, and lateral septum. It is hypothesized that these regions are componen ts of a circuit in the rat brain related to anxiety or distress. To de termine the potential relationship between generalized arousal and the observed induction of Fos-LI in the anxiety models, rats were tested in a non-aversive situation involving marked behavioral activation. Ac cordingly, after vigorous bar pressing behavior for reinforcement with sweetened condensed milk, induction of Fos-LI was minimal and compara ble to that in unhandled control rats. These latter data indicate that the distinctive neuroanatomical patterns of Fos-LI observed in the pa radigms related to anxiety were not simply due to generalized behavior al activation. In summary, select common brain regions were identified that express Fos-LI in empirical models of anxiety. These data provid e a functional framework to explore neuroanatomical sites of action of psychotherapeutic drugs that influence behavioral responses in these tasks.