Role of dopamine receptor mechanisms in the amygdaloid modulation of fear and anxiety: Structural and functional analysis

Mora, Miguel Pérez de la; Gallegos-Cari, Andrea; Arizmendi-García, Yexel; Marcellino, Daniel; Fuxé, Kjell

doi:10.1016/j.pneurobio.2009.10.010

Cited by 256 publications

(145 citation statements)

References 265 publications

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“…D2R expression is high in CeA, as it is in the interconnected structures of bed nucleus of stria terminalis and nucleus accumbens (central extended AMYG) and dorsal striatum-external pallidum (Alheid and Heimer, 1988). D2R antagonism, including in the CeA specifically, has been demonstrated to decrease two-way avoid-escape and increase fear (Perez de la Mora et al, 2010;Reis et al, 2004). The D2R interacts antagonistically with the adenosine receptor A2AR by forming heteromers (Boison et al, 2012); because expression of both Drd2 and Adora2a was decreased by CSD it is difficult to predict the functional consequences; nonetheless it is noteworthy that striatum-specific Adora2a knockout mice exhibited decreased activity and two-way avoid-escape (Singer et al, 2013), as observed in CSD mice.…”

Section: Discussionmentioning

confidence: 99%

Mouse social stress induces increased fear conditioning, helplessness and fatigue to physical challenge together with markers of altered immune and dopamine function

et al. 2014

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In neuropsychiatry, animal studies demonstrating causal effects of environmental manipulations relevant to human aetiology on behaviours relevant to human psychopathologies are valuable. Such valid models can improve understanding of aetio-pathophysiology and preclinical discovery and development of new treatments. In depression, specific uncontrollable stressful life events are major aetiological factors, and subsequent generalized increases in fearfulness, helplessness and fatigue are core symptoms or features. Here we exposed adult male C57BL/6 mice to 15-day psychosocial stress with loss of social control but minimal physical wounding. One cohort was assessed in a 3-day test paradigm of motor activity, fear conditioning and 2-way avoid-escape behaviour on days 16-18, and a second cohort was assessed in a treadmill fatigue paradigm on days 19 and 29, followed by the 3-day paradigm on days 30-32. All tests used a physical aversive stimulus, namely mild, brief electroshocks. Socially stressed mice displayed decreased motor activity, increased fear acquisition, decreased 2-way avoid-escape responding (increased helplessness) and increased fatigue. They also displayed increased plasma TNF and spleen hypertrophy, and adrenal hypertrophy without hyper-corticoidism. In a third cohort, psychosocial stress effects on brain gene expression were assessed using next generation sequencing. Gene expression was altered in pathways of inflammation and G-protein coupled receptors in prefrontal cortex and amygdala; in the latter, expression of genes important in dopamine function were de-regulated including down-regulated Drd2, Adora2a and Darpp-32. This model can be applied to identify targets for treating psychopathologies such as helplessness or fatigue, and to screen compounds/biologics developed to act at these targets. AbstractIn neuropsychiatric research, animal studies that demonstrate causal effects of environmental manipulations relevant to human aetiological factors on emotional and cognitive behaviours relevant to human psychopathologies are valuable. Such valid animal models can be useful for improved understanding of aetio-pathophysiology and preclinical discovery and development of new treatments. In depression, specific uncontrollable stressful life events are major aetiological factors, and subsequent generalized increases in fearfulness, helplessness and fatigue are core psychopathology symptoms or features. In the present study we exposed adult male C57BL/6 mice to an environmental manipulation of 15-day psychosocial stress with loss of social control but with minimal physical wounding. One cohort of stressed and control mice was assessed in a novel 3-day test paradigm of motor activity, fear conditioning and 2-way avoid-escape behaviour on days 16-18, and a second cohort was assessed in a treadmill fatigue paradigm on days 19 and 29, followed by the 3-day paradigm on days 30-32. All tests used a physical aversive stimulus, namely mild, brief electroshocks. The socially stressed mice displayed dec...

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Section: Discussionmentioning

confidence: 99%

Mouse social stress induces increased fear conditioning, helplessness and fatigue to physical challenge together with markers of altered immune and dopamine function

et al. 2014

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“…Systemic and local applications into the amygdala of D1 agonist and antagonist are known to potentiate and decrease fear response in animals, respectively. Although some studies reported that applications of D2 agonist and antagonist induced similar effects, the results were less consistent compared with D1-mediated effects (for review, see Pezze and Feldon, 2004;de la Mora et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Contribution of Dopamine D1 and D2 Receptors to Amygdala Activity in Human

Takahashi¹,

Takano²,

Kodaka³

et al. 2010

J. Neurosci.

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Several animal studies have demonstrated functional roles of dopamine (DA) D1 and D2 receptors in amygdala activity. However, the contribution of DA D1 and D2 receptors to amygdala response induced by affective stimuli in human is unknown. To investigate the contribution of DA receptor subtypes to amygdala reactivity in human, we conducted a multimodal in vivo neuroimaging study in which DA D1 and D2 receptor bindings in the amygdala were measured with positron emission tomography (PET), and amygdala response induced by fearful faces was assessed by functional magnetic resonance imaging (fMRI) in healthy volunteers. We used multimodality voxelwise correlation analysis between fMRI signal and DA receptor binding measured by PET. DA D1 binding in the amygdala was positively correlated with amygdala signal change in response to fearful faces, but DA D2 binding in the amygdala was not related to amygdala signal change. DA D1 receptors might play a major role in enhancing amygdala response when sensory inputs are affective.

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“…Ventral tegmental area projection to the BLA Many dopamine neurons innervating the BLA originate from cells situated within multiple subgroups of the ventral tegmental area (VTA) (de la Mora et al 2010). Dopamine is frequently associated with reward: both unexpected rewards and cues that predict rewards trigger phasic firing in 75% of dopaminergic VTA neurons (Romo and Schultz 1990;Schultz 2007).…”

Section: Org Downloaded Frommentioning

confidence: 99%

“…Because D5 receptors have higher affinity for dopamine, it has been suggested that dopamine presynaptic actions may predominate in the BLA at low levels of dopamine, while postsynaptic effects increase and dominate as dopaminergic drive increases. Dopamine type 2 receptors (D2) have also been observed in the BLA (Maltais et al 2000), but the localization of these receptors is unclear and the level of expression of D2 receptors is controversial (de la Mora et al 2010).…”

Section: Org Downloaded Frommentioning

confidence: 99%

“…Providing further support, both D1 receptor antagonism and genetic ablation of D1 receptors in the BLA impair the acquisition of fear memories (Greba and Kokkinidis 2000;Fadok et al 2009). The role of the D2 receptor in BLA-dependent aversive memory is far less studied, but (Lalumiere et al 2004) and also inhibits the acquisition of fear potentiated startle (de la Mora et al 2010).…”

Section: Org Downloaded Frommentioning

confidence: 99%

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Input-specific contributions to valence processing in the amygdala

Correia

Goosens

2016

Learn. Mem.

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Reward and punishment are often thought of as opposing processes: rewards and the environmental cues that predict them elicit approach and consummatory behaviors, while punishments drive aversion and avoidance behaviors. This framework suggests that there may be segregated brain circuits for these valenced behaviors. The basolateral amygdala (BLA) is one brain region that contributes to both types of motivated behavior. Individual neurons in the BLA can favor positive over negative valence, or vice versa, but these neurons are intermingled, showing no anatomical segregation. The amygdala receives inputs from many brain areas and current theories posit that encoding of positive versus negative valence by BLA neurons is determined by the wiring of each neuron. Specifically, many projections from other brain areas that respond to positive and negative valence stimuli and predictive cues project strongly to the BLA and likely contribute to valence processing within the BLA. Here we review three of these areas, the basal forebrain, the dorsal raphe nucleus and the ventral tegmental area, and discuss how these may promote encoding of positive and negative valence within the BLA.The basic desire to seek reward and avoid punishment shapes virtually all of behavior, and the ability to discriminate between "good" and "bad" environmental cues is critical for guiding choices and maximizing survival. Thus, understanding the brain circuits that encode motivated behaviors is important because it contributes to our knowledge of how we learn, and it is also essential for understanding human disorders associated with abnormal processing of reward and danger (i.e., emotional disorders), such as anxiety, depression, addiction, and post-traumatic stress disorder (PTSD).The amygdala is one brain area implicated in motivated behaviors and the basolateral complex of the amygdala (BLA) receives information about diverse environmental stimuli from many brain regions. The BLA is thought to encode the association of predictive stimuli with both aversive and appetitive outcomes (Morrison and Salzman 2010;Barberini et al. 2012). Reward and punishment are reinforcers of opposite valence (positive versus negative), and these reinforcers typically lead to opposing behaviors (approach versus avoidance). Many theories have suggested that appetitive and aversive systems act in opponent fashion (Solomon and Corbit 1974;Daw et al. 2002). However, it is unclear how the BLA contributes to this. We do not yet understand the extent to which aversive and appetitive information is processed in parallel BLA circuits, or whether individual BLA neurons are involved in the regulation of both types of motivated behaviors.In this review, we propose several models by which functional segregation of valence can be achieved in the BLA. These models are based on studies describing how BLA neurons respond to reward and aversive stimuli. We then consider whether three major inputs, known to carry valenced information, support or conflict these models, and also discus...

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Role of dopamine receptor mechanisms in the amygdaloid modulation of fear and anxiety: Structural and functional analysis

Cited by 256 publications

References 265 publications

Mouse social stress induces increased fear conditioning, helplessness and fatigue to physical challenge together with markers of altered immune and dopamine function

Mouse social stress induces increased fear conditioning, helplessness and fatigue to physical challenge together with markers of altered immune and dopamine function

Contribution of Dopamine D1 and D2 Receptors to Amygdala Activity in Human

Input-specific contributions to valence processing in the amygdala

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