Year-end Sale % OFF 
Abstract
The central nucleus of the amygdala (CeA) is involved in the expression of fear and has been implicated in several anxiety disorders. This structure is densely innervated by DAergic projections that impinge on amygdalar neurons expressing various dopamine (DA) receptor subtypes, including D2 receptors (D2Rs). Although various pharmacological approaches have assessed the role of D2Rs in the CeA, the actual participation of postsynaptic D2Rs in the CeA to defensive behaviors remains unclear. Here, we investigated the distribution of D2Rs in the CeA and their role in modifying neuronal activity and fear related behaviors in mice. First, using the mouse reporter strain D2R-EGFP, we verified that D2Rs are present both in neurons of the CeA and in A10 dorsocaudal (A10dc) DAergic neurons that innervate the CeA. Moreover, we showed that pharmacological stimulation of D2Rs increases the activity of protein kinase C (PKC)δ cells present in the CeA, a type of neuron previously associated with reduced defensive behaviors. Finally, using a molecular genetics approach that discriminates postsynaptic D2Rs from presynaptic D2 autoreceptors, we demonstrated that mice carrying targeted deletions of postsynaptic D2Rs in the CeA display increased risk avoidance in exploratory tasks. Together, our results indicate that postsynaptic D2Rs in the CeA attenuate behavioral reactions to potential environmental threats.
Highlights
The central nucleus of the amygdala (CeA) is involved in the expression of fear and has been implicated in several anxiety disorders. This structure is densely innervated by dopaminergic projections that impinge on amygdalar neurons expressing various dopamine receptor subtypes, including D2 receptors (D2Rs)
Using these triple transgenic mice, we found that D2R expressing neurons and DAergic fibers largely overlap in the CeL (Fig. 1B), suggesting that D2Rs of the CeA are functional receptors regulated by DA
The enhanced avoidance behavior observed in mice partially lacking D2Rs in the CeA was more profound when mice were studied in the dark-light box test than in the elevated plus maze
Summary
Fear, and threat avoidance are highly conserved adaptive behaviors that are essential for fitness and survival. Fear responses appear as exaggerated behavioral reactions to stimuli that do not represent a commensurate threat, underling symptoms of pathological conditions such as anxiety and post-traumatic disorders. The dopamine (DA) D2 receptor gene (DRD2) is expressed in the CeA of rodents (Scibilia et al, 1992; Kim et al, 2017; McCullough et al, 2018a, 2018b) and humans (Gurevich et al, 1999; Xiang et al, 2008). DA D2 receptors (D2Rs) present in the CeA have been implicated in impulsive behaviors (Kim et al,, 2018) whereas several association human studies have linked particular genetic polymorphisms of DRD2 with avoidance behavior (Frank and Hutchison, 2009), social phobia (Schneier et al, 2000), social dysfunction (Lawford et al, 2006) and anxiety-driven alcoholism (Joe et al, 2008). Given the involvement of the CeA in defensive behaviors, and its regulation by DA, we hypothesized that D2Rs in the CeA regulate behavioral responses to potential threats, and that ablation of postsynaptic D2Rs in the mouse CeA would increase avoidance behaviors
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
