Distinct patterns of brain Fos expression in Carioca High- and Low-conditioned Freezing Rats

Abstract

Background The bidirectional selection of high and low anxiety-like behavior is a valuable tool for understanding the neurocircuits that are responsible for anxiety disorders. Our group developed two breeding lines of rats, known as Carioca High-and Low-conditioned Freezing (CHF and CLF), based on defensive freezing in the contextual fear conditioning paradigm. A random selected line was employed as a control (CTL) comparison group for both CHF and CLF lines of animals. The present study performed Fos immunochemistry to investigate changes in neural activity in different brain structures among CHF and CLF rats when they were exposed to contextual cues that were previously associated with footshock. Results The study indicated that CHF rats expressed high Fos expression in the locus coeruleus, periventricular nucleus of the hypothalamus (PVN), and lateral portion of the septal area and low Fos expression in the medial portion of the septal area, dentate gyrus, and prelimbic cortex (PL) compared to CTL animals. CLF rats exhibited a decrease in Fos expression in the PVN, PL, and basolateral nucleus of the amygdala and increase in the cingulate and perirhinal cortices compared to CTL animals. Conclusions Both CHF and CLF rats displayed Fos expression changes key regions of the anxiety brain circuitry. The two bidirectional lines exhibit different pattern of neural activation and inhibition with opposing influences on the PVN, the main structure involved in regulating the hypothalamic-pituitary-adrenal neuroendocrine responses observed in anxiety disorders.

An animal model of trait anxiety: Carioca high freezing rats as a model of generalized anxiety disorder

“…Finally, other studies developed by our group but not discussed in the scope of this review (for details, see Dias et al, 2014 ; Lages et al, 2023 ; Léon et al, 2020 ) also indicate functional and structural changes in neural circuits underlying anxiety in the CHF rat line, which seems to indicate that the phenotyping process that strengthened this trait anxiety was also expressed in terms of a great capacity for neural plasticity.…”

Systemic Chronic Treatment with Cannabidiol in Carioca High- and Low-Conditioned Freezing Rats in the Neuropathic Pain Model: Evaluation of Pain Sensitivity

“…Our data revealed that treatment of CBD produced different effects on neuropathic pain in individuals with distinct anxiety levels (CLF, CTL, CHF lineages). The lineages did not show basal differences, confirming that nociceptive stimuli did not select these lineages [ 36 , 42 ]. Moreover, a lower efficacy of CBD was observed in the CHF+CCI group compared to the CTL+CCI in mechanical and cold thermal sensitivity, which suggests the hypothesis of an elevated level of sensitivity in this lineage.…”

Non-human contributions to personality neuroscience: From fish through primates – a concluding editorial overview

“…Their Table 1 maps CHF rats to human generalized anxiety in terms of (their words): 1) High and diffuse anxiety in contextual fear conditioning, elevated plus maze, and avoidance behavior in the elevated T-maze; 2) Immobility/freezing behavior; 3) Different pattern of acquisition/extinction in response to context and cue; 4) Increased corticosterone serum levels; 5) Benzodiazepine and serotonergic anxiolytics attenuate freezing behavior in CHF but not CLF rats; and 6) Higher alcohol intake. CHF rats have also shown parallel changes in the function and structure of neural circuits thought to underlie anxiety (Dias et al, 2014 ; Lages et al, 2023 ; León et al, 2020 ).…”