The Carioca High and Low Conditioned Freezing Lines: A New Animal Model of Generalized Anxiety Disorder

Gomes, Vítor de Castro; Silva, Carlos Eduardo Barroso; Landeira-Fernández, J.

doi:10.5772/23598

Cited by 9 publications

(5 citation statements)

References 71 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The results of our ongoing breeding program have shown a clear divergence of the conditioned freezing phenotype after only three generations (Castro-Gomes and Landeira-Fernandez, 2008 ). The presence of different levels of anxiety-like behavior, that are characteristic of each line, can be assessed using several behavioral tests, including the elevated plus maze (EPM), the social interaction test and defensive responses that are induced by electrical stimulation of the dorsal periaqueductal gray (Dias et al, 2009 ; Galvão et al, 2010 ; Castro-Gomes et al, 2011 , 2014 ; Salviano et al, 2014 ). These two lines represent an important tool for investigating the anxiogenic/anxiolytic pharmacological profiles of various compounds (Castro-Gomes et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Behavioral Effects of Systemic, Infralimbic and Prelimbic Injections of a Serotonin 5-HT2A Antagonist in Carioca High- and Low-Conditioned Freezing Rats

León

Castro-Gomes

Zárate-Guerrero

et al. 2017

Front. Behav. Neurosci.

Self Cite

View full text Add to dashboard Cite

The role of serotonin (5-hydroxytryptamine [5-HT]) and 5-HT2A receptors in anxiety has been extensively studied, mostly without considering individual differences in trait anxiety. Our laboratory developed two lines of animals that are bred for high and low freezing responses to contextual cues that are previously associated with footshock (Carioca High-conditioned Freezing [CHF] and Carioca Low-conditioned Freezing [CLF]). The present study investigated whether ketanserin, a preferential 5-HT2A receptor blocker, exerts distinct anxiety-like profiles in these two lines of animals. In the first experiment, the animals received a systemic injection of ketanserin and were exposed to the elevated plus maze (EPM). In the second experiment, these two lines of animals received microinjections of ketanserin in the infralimbic (IL) and prelimbic (PL) cortices and were exposed to either the EPM or a contextual fear conditioning paradigm. The two rat lines exhibited bidirectional effects on anxiety-like behavior in the EPM and opposite responses to ketanserin. Both systemic and intra-IL cortex injections of ketanserin exerted anxiolytic-like effects in CHF rats but anxiogenic-like effects in CLF rats. Microinjections of ketanserin in the PL cortex also exerted anxiolytic-like effects in CHF rats but had no effect in CLF rats. These results suggest that the behavioral effects of 5-HT2A receptor antagonism might depend on genetic variability associated with baseline reactions to threatening situations and 5-HT2A receptor expression in the IL and PL cortices.Highlights CHF and CLF rats are two bidirectional lines that are based on contextual fear conditioning.CHF rats have a more “anxious” phenotype than CLF rats in the EPM.The 5-HT2A receptor antagonist ketanserin had opposite behavioral effects in CHF and CLF rats.Systemic and IL injections either decreased (CHF) or increased (CLF) anxiety-like behavior.PL injections either decreased (CHF) anxiety-like behavior or had no effect (CLF).

show abstract

Section: Introductionmentioning

confidence: 99%

Behavioral Effects of Systemic, Infralimbic and Prelimbic Injections of a Serotonin 5-HT2A Antagonist in Carioca High- and Low-Conditioned Freezing Rats

León

Castro-Gomes

Zárate-Guerrero

et al. 2017

Front. Behav. Neurosci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The hippocampus is a crucial structure for contextual fear learning, which is in turn considered an appropriate paradigm for establishing animal models of GAD [2,13,14]. The present work investigated biomarkers of hippocampal plasticity in the Carioca High-Conditioned Freezing rats (CHF), an established and validated animal model of generalized anxiety.…”

Section: Introductionmentioning

confidence: 99%

Hippocampal biomarkers of fear memory in an animal model of generalized anxiety disorder

Dias

Bevilaqua

Luz

et al. 2014

Behavioural Brain Research

View full text Add to dashboard Cite

Generalized anxiety disorder (GAD) is highly prevalent and incapacitating. Here we used the Carioca High-Conditioned Freezing (CHF) rats, a previously validated animal model for GAD, to identify biomarkers and structural changes in the hippocampus that could be part of the underlying mechanisms of their high-anxiety profile. Spatial and fear memory was assessed in the Morris water maze and passive avoidance test. Serum corticosterone levels, immunofluorescence for glucocorticoid receptors (GR) in the dentate gyrus (DG), and western blotting for hippocampal brain derived neurotrophic factor (BDNF) were performed. Immunohistochemistry for markers of cell proliferation (bromodeoxiuridine/Ki-67), neuroblasts (doublecortin), and cell survival were undertaken in the DG, along with spine staining (Golgi) and dendritic arborization tracing. Hippocampal GABA release was assessed by neurochemical assay. Fear memory was higher among CHF rats whilst spatial learning was preserved. Serum corticosterone levels were increased, with decreased GR expression. No differences were observed in hippocampal cell proliferation/survival, but the number of newborn neurons was decreased, along with their number and length of tertiary dendrites. Increased expression of proBDNF and dendritic spines was observed; lower ratio of GABA release in the hippocampus was also verified. These findings suggest that generalized anxiety/fear could be associated with different hippocampal biomarkers, such as increased spine density, possibly as a compensatory mechanism for the decreased hippocampal number of neuroblasts and dendritic arborization triggered by high corticosterone. Disruption of GABAergic signaling and BDNF impairment are also proposed as part of the hippocampal mechanisms possibly underlying the anxious phenotype of this model.

show abstract

“…As expected, CHF, CTL, and CLF animals exhibited different levels of defensive freezing behavior that was induced by stimuli that were contextually associated with footshock on the previous day. These results indicated that our breeding protocol effectively produced different levels of freezing and confirmed that CHF animals had a higher anxious phenotype and CLF animals had a lower anxious phenotype when both breeding lines were compared to CTL animals [ 31 ]. Our results indicate that both CHF and CLF animals exhibited clear differences in Fos immunoreactivity in certain brain structures compared to randomly selected CTL animals.…”

Section: Discussionmentioning

confidence: 66%

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

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.

show abstract

The Carioca High and Low Conditioned Freezing Lines: A New Animal Model of Generalized Anxiety Disorder

Cited by 9 publications

References 71 publications

Behavioral Effects of Systemic, Infralimbic and Prelimbic Injections of a Serotonin 5-HT2A Antagonist in Carioca High- and Low-Conditioned Freezing Rats

Behavioral Effects of Systemic, Infralimbic and Prelimbic Injections of a Serotonin 5-HT2A Antagonist in Carioca High- and Low-Conditioned Freezing Rats

Hippocampal biomarkers of fear memory in an animal model of generalized anxiety disorder

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

Contact Info

Product

Resources

About