ABSTRACT
Behavioral and molecular characterization of cell- type specific populations governing fear learning and behavior is a promising avenue for the rational identification of potential therapeutics for fear-related disorders. Identification of cell-type specific changes in neuronal translation following fear learning allows for targeted pharmacological intervention during fear extinction learning, mirroring possible treatment strategies in humans. Here we identify the central amygdala (CeA) Drd2-expressing population as a fear-supporting population that is molecularly distinct from other, previously identified fear-supporting CeA populations. Sequencing of actively translating transcripts of Drd2 neurons identifies mRNAs that are differentially regulated following fear learning including Npy5r, Rxrg, Sst5r, Fgf3, ErbB4, Fkbp14, Dlk1,Ssh3 and Adora2a. Direct pharmacological manipulation of NPY5R, RXR, and ADORA2A confirms their importance in fear behavior and validates the present approach of identifying pharmacological targets for the modulation of emotional learning.
ABSTRACT
BACKGROUND: The melanocortin 4 receptor (MC4R) is involved in the regulation of homeostatic energy balance by the hypothalamus. Recent reports showed that MC4R can also control the motivation for food in association with a brain reward system, such as dopamine. We investigated the expression levels of MC4R and the dopamine D2 receptor (D2R), which is known to be related to food rewards, in both the hypothalamus and brain regions involved in food rewards. METHODS: We examined the expression levels of D2R and MC4R by dual immunofluorescence histochemistry in hypothalamic regions and in the bed nucleus of the stria terminalis (BNST), the central amygdala, and the ventral tegmental area of transgenic mice expressing enhanced green fluorescent protein under the control of the D2R gene. RESULTS: In the hypothalamic area, significant coexpression of MC4R and D2R was observed in the arcuate nucleus. We observed a significant coexpression of D2R and MC4R in the BNST, which has been suggested to be an important site for food reward. CONCLUSION: We suggest that MC4R and D2R function in the hypothalamus for control of energy homeostasis and that within the brain regions related with rewards, such as the BNST, the melanocortin system works synergistically with dopamine for the integration of food motivation in the control of feeding behaviors.
Subject(s)
Animals , Mice , Amygdala , Arcuate Nucleus of Hypothalamus , Brain , Dopamine , Eating , Feeding Behavior , Fluorescent Antibody Technique , Homeostasis , Hypothalamus , Mice, Transgenic , Motivation , Obesity , Receptor, Melanocortin, Type 4 , Receptors, Dopamine D2 , Reward , Ventral Tegmental AreaABSTRACT
Objective To study the modulation of central amygdale (CeA)on cardiac nociception with electrical stimulation in rats.Methods The heart pain model of adult male Sprague-Dawley rats was established with intrapericardial injection of capsaicin; then the evoked electromyography (EMG ) responses in the spinotrapezius (SPT)were observed as an index.Immunohistochemical method was used to observe the expression of c-fos in CeA;The rats were divided into normal control group,intrapericardial saline injection control group,and intrapericardial capsaicin injection group. The changes of EMG responses after electrical stimulation on CeA (intensity of 30μA and 70μA)were observed separately by electrophysiology in different groups.Results① Compared with normal control group, intrapericardial capsaicin injection group had significantly increased expression of c-fos in CeA.However,c-fos expression did not differ significantly between intrapericardial saline injection group and normal control group;② After 30μA electrical stimulation on CeA,EMG response in SPT significantly decreased in intrapericardial capsaicin injection group compared with that in control group;the total discharge rate was (78.58±4.62)% of that of control group (P<0.05).After 70μA electrical stimulation on CeA, the total discharge rate was (54.89±3.98)% of that of control group (P<0.05).Conclusion CeA may be involved in cardiac nociceptive transmission in rats and has inhibitory effects on the modulation of rat cardiac nociception.