Pharmacological and Physiological Correlates of the Bidirectional Fear Phenotype of the Carioca Rats and Other Bidirectionally Selected Lines

Abstract

The Carioca rat lines originated from the selective bidirectional breeding of mates displaying extreme defense responses to contextual conditioned fear. After three generations, two distinct populations could be distinguished: the Carioca High- and Low-conditioned Freezing rats, CHF, and CLF, respectively. Later studies identified strong anxiety-like behaviors in the CHF line, while indications of impulsivity and hyperactivity were prominent in the CLF animals. The present review details the physiological and pharmacological-related findings obtained from these lines. The results discussed here point towards a dysfunctional fear circuitry in CHF rats, including alterations in key brain structures and the serotoninergic system. Moreover, data from these animals highlight important alterations in the stress-processing machinery and its associated systems, such as energy metabolism and antioxidative defense. Finally, evidence of an alteration in the dopaminergic pathway in CLF rats is also debated. Thus, accumulating data gathered over the years, place the Carioca lines as significant animal models for the study of psychiatric disorders, especially fear-related ones like anxiety.

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.…”

Neuroinflammation in the prefrontal-amygdala-hippocampus network is associated with maladaptive avoidance behaviour

“…Interestingly, increased TNF-ɑ in the AMG is associated with altered levels of glutamate in this same nucleus, disturbances in learning and increased fear responses, which can contribute to the impaired fear extinction seen in psychiatric disorders [ 23 , 38 ]. Indeed, increased EAAT-2 expression (a major glutamate transporter expressed predominantly in astrocytes) has been reported in association with increased fear responses and is relevant to psychiatric and neurological disorders [ 39 , 40 ]. In line with these findings, our study observed increased astrocyte and EAAT-2 expression in the amygdala of MA animals, suggesting altered these to be involved in the presentation of maladaptive avoidance behaviour and expression of exacerbated fear responses.…”

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

“…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).…”

“…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 ).…”