Role of the Basolateral Nucleus of the Amygdala in the Formation of a Phobia

File, Sandra E.; González, L.; Gallant, Rachael

doi:10.1016/s0893-133x(98)00035-9

Cited by 83 publications

(43 citation statements)

References 25 publications

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“…It is significant that the enhanced anxiety is associated with a reduced threshold for synaptic plasticity in the amygdala, principally in adult female mice. A large body of evidence indicates that the amygdala is important to anxiety and fear for both sexes in rodents (16,39,40) and humans (41). A reduced threshold for synaptic enhancement in this structure could result in exaggerated responses to normally innocuous stimuli or environments, a characteristic feature of fear and anxiety disorders.…”

Section: Discussionmentioning

confidence: 99%

“…Although the exact mode of action by which estrogen exerts its diverse effects is not clear, it is almost certain that the inhibitory neurotransmitter ␥-aminobutyric acid (GABA) is involved (13, 14, ¶). GABA is implicated in fear and anxiety, on the evidence of both pharmacological (15,16) and gene-targeting (17,18) experiments. Regulation of the expression of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD) by ERs (13, ¶, 19) may be crucial to modulation of GABA type A activity and, therefore, to fear and anxiety.…”

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confidence: 99%

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Increased anxiety and synaptic plasticity in estrogen receptor β-deficient mice

Krężel

Dupont

Krust

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

258

185

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Estrogens are powerful modulators of neuronal physiology and in humans may affect a broad range of functions, including reproductive, emotional, and cognitive behaviors. We studied the contribution of estrogen receptors (ERs) in modulation of emotional processes and analyzed the effects of deleting ER␣ or ER␤ in mice. Behavior consistent with increased anxiety was observed principally in ER␤ mutant females and was associated with a reduced threshold for the induction of synaptic plasticity in the basolateral amygdala. Local increase of 5-hydroxytryptamine 1a receptor expression in medial amygdala may contribute to these changes. Our data show that, particularly in females, there is an important role for ER␤-mediated estrogen signaling in the processing of emotional behavior. There is a strong link between estrogen and emotional disturbances in humans. Mood fluctuations, depression, irritability, and anxiety have often been associated with low levels of estradiol in postmenopausal women (1, 2), whereas estrogen replacement therapy ameliorates these psychological conditions (1-3). Reduced estrogen signaling in rodents leads to behavior indicative of increased anxiety (4, §). Little is known, however, about either the mechanisms or sites of estrogen actions in these modulatory processes, or the neurotransmitter systems involved in these regulations.In the nervous system, estrogen signals are transduced by both nuclear estrogen receptors (ER␣ and ER␤), which act as transcription factors, and by a nongenomic pathway, which has yet to be identified. Both receptors show similar patterns of expression and are found at abundance in medial amygdala, bed nucleus of stria terminalis and preoptic area, whereas in hippocampus, ER␣ is the predominant ER isotype in mouse (5). Recent analysis of reproductive and aggressive behavior in ER␣ and ER␤ null mutant mice provided the first clear evidence for a role for ERs in brain functions (6-8).High levels of estrogens have been shown to increase dendrite growth and synaptic plasticity in the rat hippocampus in vitro and in vivo (9, 10). Furthermore, the in vivo experiments revealed that estrogen enhances neuronal excitability in the hippocampus (11). In the basolateral amygdala, a structure involved in fear and anxiety, estrogens have quite the opposite effect and reduce neuronal excitability (11,12). Although the exact mode of action by which estrogen exerts its diverse effects is not clear, it is almost certain that the inhibitory neurotransmitter ␥-aminobutyric acid (GABA) is involved (13, 14, ¶). GABA is implicated in fear and anxiety, on the evidence of both pharmacological (15, 16) and gene-targeting (17, 18) experiments. Regulation of the expression of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD) by ERs (13, ¶, 19) may be crucial to modulation of GABA type A activity and, therefore, to fear and anxiety. Moreover, GABAergic tone in amygdala can be affected by serotonergic signaling (20, 21), which in turn can be downregulated by estrogen's effects on the 5-h...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Increased anxiety and synaptic plasticity in estrogen receptor β-deficient mice

Krężel

Dupont

Krust

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

258

185

View full text Add to dashboard Cite

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“…To be on an open arm seems to be an aversive experience, and inhibitory avoidance, measured as the time taken to leave the enclosed arm, might be related to GAD. On the other hand, elevated mazes primarily produce an innate fear of height and openness (Graeff et al, 1998), and might therefore be of more use in the study of phobic disorders (Bourin, 1997;File, Gonzalez, & Gallant, 1998). Furthermore, it has been put forward that repeated testing in this model might not produce stable results (Espejo, 1997;File, Zangrossi, Viana, & Graeff, 1993), ruling out withinsubjects designs and its use as a chronic model.…”

Section: Animal Models For Gadmentioning

confidence: 99%

Contextual conditioning in rats as an animal model for generalized anxiety disorder

Luyten

Vansteenwegen

Kuyck

et al. 2011

Cogn Affect Behav Neurosci

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Animal models of psychiatric disorders are important translational tools for exploring new treatment options and gaining more insight into the disease. Thus far, there is no systematically validated animal model for generalized anxiety disorder (GAD), a severely impairing and difficult-to-treat disease. In this review, we propose contextual conditioning (CC) as an animal model for GAD. We argue that this model has sufficient face validity (there are several symptom similarities), predictive validity (it responds to clinically effective treatments), and construct validity (the underlying mechanisms are comparable). Although the refinement and validation of an animal model is a never-ending process, we want to give a concise overview of the currently available evidence. We suggest that the CC model might be a valuable preclinical tool to enhance the development of new treatment strategies and our understanding of GAD.

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“…Estudos envolvendo manipulações farmacológicas e neuroanatômicas desses recetores têm recebido, portanto, atenção especial nas investigações sobre o papel da 5-HT na ansiedade. Paralelamente, evidências clínicas e experimentais indicam um papel central da amígdala na modulação de estados de ansiedade (Cruz & Landeira-Fernandez, 2001;Davis, 1986Davis, , 1998Doron & LeDoux, 1999;File, Gonzalez & Gallant, 1998;Gallager & Chiba, 1996;LeDoux, 1998;Menard & Treit, 1999).…”

Section: G a Pinheiro And Colsunclassified

Envolvimento dos receptores 5-HT2 da amígdala nos níveis de ansiedade induzidos pela exposição de ratos ao labirinto em cruz elevado

Pinheiro

Alves

Murce

et al. 2002

Psic.: Teor. e Pesq.

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O efeito de microinjeções intra-amigdalóides do antagonista 5-HT2A/2C de receptores serotoninérgicos RP 62203 (1,0; 2,5; 5,0 mg) foi investigado em medidas tradicionais e etológicas (esquadrinhar, espreitar e explorações da extremidade) de ansiedade de ratos no labirinto em cruz elevado. A dose de 5,0 mg aumentou as porcentagens de entrada e de tempo nos braços abertos, sem alterar no número de entradas nos braços fechados. As categorias esquadrinhar, espreitar e explorações da extremidade também foram alteradas pela droga. As doses de 2,5 e 5,0 mg aumentaram o tempo gasto em esquadrinhar e diminuíram o tempo gasto em espreitar. O número de explorações da extremidade também foi aumentado pela injeção da droga na dose de 5,0 mg. Este padrão comportamental sugere um efeito ansiolítico do RP 62203. A participação dos receptores 5-HT2A/2C da amígdala na regulação desse efeito é discutida.

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Role of the Basolateral Nucleus of the Amygdala in the Formation of a Phobia

Cited by 83 publications

References 25 publications

Increased anxiety and synaptic plasticity in estrogen receptor β-deficient mice

Increased anxiety and synaptic plasticity in estrogen receptor β-deficient mice

Contextual conditioning in rats as an animal model for generalized anxiety disorder

Envolvimento dos receptores 5-HT2 da amígdala nos níveis de ansiedade induzidos pela exposição de ratos ao labirinto em cruz elevado

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