RESUMEN
Genetic background may influence an individual's susceptibility to, and subsequent coping strategy for, an acute stressor. When exposed to social defeat (SD), rats bred for high (HAB) or low (LAB) trait anxiety, which also differ in depression-like behavior, showed highly divergent passive and active coping behaviors, respectively. HABs spent more time freezing and emitted more ultrasound vocalization calls during SD than LABs, which spent more time rearing and grooming. Although the behavioral data confirmed the prediction that heightened trait anxiety would make rats more prone to experience stress, adrenocorticotropin and corticosterone were secreted to a higher extent in LABs than in HABs. In the latter, Fos expression upon SD was enhanced in the amygdala and hypothalamic areas compared with LABs, whereas it was diminished in prefrontal and brainstem areas.
Asunto(s)
Adaptación Psicológica , Hormona Adrenocorticotrópica/metabolismo , Ansiedad/genética , Corticosterona/metabolismo , Genes fos/genética , Neuronas/fisiología , Conducta Social , Hormona Adrenocorticotrópica/sangre , Amígdala del Cerebelo/metabolismo , Animales , Tronco Encefálico/metabolismo , Corticosterona/sangre , Predisposición Genética a la Enfermedad , Sistema Hipotálamo-Hipofisario/metabolismo , Hipotálamo/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Corteza Prefrontal/metabolismo , Ratas , Ratas Wistar , Vocalización AnimalRESUMEN
BACKGROUND: Two Wistar rat lines selectively bred for either high (HAB) or low (LAB) anxiety-related behavior were used to identify neurobiological correlates of trait anxiety. METHODS: We used Fos expression for mapping of neuronal activation patterns in response to mild anxiety-provoking challenges. RESULTS: In both lines, exposure to an open field (OF) or the open arm (OA) of an elevated plus-maze induced Fos expression in several brain areas of the anxiety/fear circuitry. Rats of the HAB type, which showed signs of a hyperanxious phenotype and a hyperreactive hypothalamic-pituitary-adrenal axis compared with LAB rats, exhibited a higher number of Fos-positive cells in the paraventricular nucleus of the hypothalamus, the lateral and anterior hypothalamic area, and the medial preoptic area in response to both OA and OF. Less Fos expression was induced in the cingulate cortex in HAB than in LAB rats. Differential Fos expression in response to either OA or OF was observed in few brain regions, including the thalamus and hippocampus. CONCLUSIONS: The present data indicate that the divergent anxiety-related behavioral response of HAB versus LAB rats to OF and OA exposures is associated with differential neuronal activation in restricted parts of the anxiety/fear circuitry. Distinct hypothalamic regions displayed hyperexcitability, and the cingulate cortex showed hypoexcitability, which suggests that they are main candidate mediators of dysfunctional brain activation in pathologic anxiety.
Asunto(s)
Ansiedad/genética , Nivel de Alerta/genética , Encéfalo/metabolismo , Miedo/fisiología , Proteínas Proto-Oncogénicas c-fos/genética , Hormona Adrenocorticotrópica/sangre , Animales , Núcleo Hipotalámico Anterior/metabolismo , Ansiedad/psicología , Mapeo Encefálico , Expresión Génica/fisiología , Giro del Cíngulo/metabolismo , Hipocampo/metabolismo , Área Hipotalámica Lateral/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Técnicas para Inmunoenzimas , Masculino , Red Nerviosa/metabolismo , Neuronas/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Fenotipo , Área Preóptica/metabolismo , Ratas , Ratas Wistar , Selección Genética , Tálamo/metabolismoRESUMEN
BACKGROUND: The fact that induction of anxiety- and panic-related symptoms is a property common to a range of drugs suggests that common neural substrates underlie their behavioral effects. METHODS: We used Fos immunocytochemistry to test the effects of four anxiogenic drugs (FG-7142, yohimbine, m-chlorophenylpiperazine [mCPP], and caffeine) on anxiety-related circuitry in rat forebrain. RESULTS: All four drugs commonly increased Fos-like immunoreactivity in 7 of 41 brain areas investigated, namely, central nucleus of the amygdala, bed nucleus of the stria terminalis, lateral septum, paraventricular nucleus of the hypothalamus, lateral hypothalamus, infralimbic and prelimbic cortex. All drugs but one (mCPP) also increased Fos expression in the basolateral and medial amygdala, the dorsomedial hypothalamus, cingulate cortex, and parts of the motor cortex. CONCLUSIONS: The results suggest that the anxiogenic drugs selected activate a restricted set of forebrain areas. Most of these areas have previously been shown to be activated by environmentally evoked anxiety and to have anatomic connections with hindbrain regions that are activated by the same drugs and by environmentally evoked anxiety. Together, these data are consistent with the theory of an integrated forebrain and hindbrain neuronal system that is important for anxiety states evoked by both drug and environmental manipulations.