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

Despite being one of the main components of anxiety and playing a pivotal role in how an individual perceives and copes with anxiogenic situations or responds to a given treatment, trait anxiety is paradoxically omitted in most animal models of anxiety. This is problematic and particularly more concerning in models that are used to screen drugs and other treatments for specific anxiety disorders and to investigate their neurobiological mechanisms. Our group has been engaged in the search for specific anxiety-related traits in animal models of anxiety. We developed two new lines of rats with strong phenotypic divergence for high (Carioca High-conditioned Freezing [CHF]) and low (Carioca Low-conditioned Freezing [CLF]) trait anxiety as expressed in the contextual fear conditioning paradigm. Here, we summarize key behavioral, pharmacological, physiological, and neurobiological differences in one these lines, the CHF rat line, relative to randomized-cross controls and discuss how far they represent a valid and reliable animal model of generalized anxiety disorder and so high trait anxiety.

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

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.

High- and Low-conditioned Behavioral effects of midazolam in Carioca high- and low-conditioned freezing rats in an ethologically based test.

The selective breeding of laboratory rodents with different anxiety-related traits is the subject of growing interest. The present study compared the effects of the benzodiazepine midazolam in the elevated plus maze (EPM) test of anxiety in two lines of Wistar rats that were selectively bred in our laboratory for either high or low anxiety-like traits based on a contextual freezing conditioning paradigm. After phenotyping anxiety-like traits (i.e., conditioned freezing behavior), Carioca High-Freezing [CHF], Carioca Low-Freezing [CLF]) and control rats were intraperitoneally injected (1.0 ml/kg) with .9 % saline or midazolam (.25, .5, .75, and 1.0 mg/kg) and subjected to the EPM 30 min later. After the saline injection, the CHF and CLF groups exhibited lower and higher open-arm exploration in the EPM, respectively, compared with control rats. These results indicate that anxiety-related traits previously selected from an associative learning paradigm can also be phenotypically expressed in an ethologically based animal model of anxiety. All midazolam doses significantly increased open-arm exploration in both CHF and control animals, but this anxiolytic-like effect in CLF rats was only observed at the lowest dose tested (.25 mg/kg). The present findings indicate that these two breeding lines of rats are a useful model for studying anxiety, and the anxiolytic effect of midazolam depends on genetic variability that is associated with basal reactions to threatening situations.

Therapeutic effect of transcranial direct current stimulation on neuropsychological symptoms of an elderly patient: A case report.

Although growing evidence points to the potential therapeutic effects of transcranial Direct Current Stimulation (tDCS), there is still no consensus on the most appropriate protocol to be used in specific neurological and neuropsychological symptoms. This case report evaluated the neuromodulatory therapeutic effects of two 15-day courses of tDCS on an elderly female patient, aged 78 years with mild neurocognitive disorder, chronic pain and depression-related symptoms. Results indicated an overall significant improvement of cognitive and executive functions, as well as reduction in both depression and chronic pain symptoms. These results highlight the potential of tDCS as a safe and useful neuromodulatory clinical tool in the rehabilitation of elderly patients.

Embora evidências crescentes apontem para os potenciais efeitos terapêuticos da estimulação transcraniana por corrente contínua (ETCC), ainda não há consenso sobre o protocolo mais adequado a ser usado em sintomas neurológicos e neuropsicológicos específicos. Este relato de caso avaliou os efeitos terapêuticos neuromoduladores de dois protocolos de 15 dias de ETCC em paciente idosa, com idade de 78 anos com comprometimento cognitivo leve, dor crônica e sintomas relacionados à depressão. Os resultados indicaram uma melhoria global significativa das funções cognitivas e executivas, bem como a redução tanto na depressão quanto nos sintomas da dor crônica. Isso destaca o potencial do ETCC como uma ferramenta clínica neuromoduladora segura e útil na reabilitação de pacientes idosos.

Therapeutic effect of transcranial direct current stimulation on neuropsychological symptoms of an elderly patient: A case report / Efeito terapêutico da estimulação transcraniana de corrente direta nos sintomas neuropsicológicos de um paciente idoso: relato de caso

ABSTRACT Although growing evidence points to the potential therapeutic effects of transcranial Direct Current Stimulation (tDCS), there is still no consensus on the most appropriate protocol to be used in specific neurological and neuropsychological symptoms. This case report evaluated the neuromodulatory therapeutic effects of two 15-day courses of tDCS on an elderly female patient, aged 78 years with mild neurocognitive disorder, chronic pain and depression-related symptoms. Results indicated an overall significant improvement of cognitive and executive functions, as well as reduction in both depression and chronic pain symptoms. These results highlight the potential of tDCS as a safe and useful neuromodulatory clinical tool in the rehabilitation of elderly patients.

RESUMO Embora evidências crescentes apontem para os potenciais efeitos terapêuticos da estimulação transcraniana por corrente contínua (ETCC), ainda não há consenso sobre o protocolo mais adequado a ser usado em sintomas neurológicos e neuropsicológicos específicos. Este relato de caso avaliou os efeitos terapêuticos neuromoduladores de dois protocolos de 15 dias de ETCC em paciente idosa, com idade de 78 anos com comprometimento cognitivo leve, dor crônica e sintomas relacionados à depressão. Os resultados indicaram uma melhoria global significativa das funções cognitivas e executivas, bem como a redução tanto na depressão quanto nos sintomas da dor crônica. Isso destaca o potencial do ETCC como uma ferramenta clínica neuromoduladora segura e útil na reabilitação de pacientes idosos.