Publication Date:
2012-07-13
Description:
Chronic stress is a strong diathesis for depression in humans and is used to generate animal models of depression. It commonly leads to several major symptoms of depression, including dysregulated feeding behaviour, anhedonia and behavioural despair. Although hypotheses defining the neural pathophysiology of depression have been proposed, the critical synaptic adaptations in key brain circuits that mediate stress-induced depressive symptoms remain poorly understood. Here we show that chronic stress in mice decreases the strength of excitatory synapses on D1 dopamine receptor-expressing nucleus accumbens medium spiny neurons owing to activation of the melanocortin 4 receptor. Stress-elicited increases in behavioural measurements of anhedonia, but not increases in measurements of behavioural despair, are prevented by blocking these melanocortin 4 receptor-mediated synaptic changes in vivo. These results establish that stress-elicited anhedonia requires a neuropeptide-triggered, cell-type-specific synaptic adaptation in the nucleus accumbens and that distinct circuit adaptations mediate other major symptoms of stress-elicited depression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397405/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397405/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lim, Byung Kook -- Huang, Kee Wui -- Grueter, Brad A -- Rothwell, Patrick E -- Malenka, Robert C -- F32 MH096491/MH/NIMH NIH HHS/ -- P01 DA008227/DA/NIDA NIH HHS/ -- England -- Nature. 2012 Jul 11;487(7406):183-9. doi: 10.1038/nature11160.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22785313" target="_blank"〉PubMed〈/a〉
Keywords:
Anhedonia/*physiology
;
Animals
;
Behavior, Animal/drug effects/physiology
;
Cocaine/pharmacology
;
Depression/pathology
;
Dopamine Uptake Inhibitors/pharmacology
;
Electrical Synapses/genetics/*metabolism
;
Feeding Behavior/physiology
;
Gene Knockdown Techniques
;
Mice
;
Nucleus Accumbens/*pathology
;
Receptor, Melanocortin, Type 4/genetics/*metabolism
;
*Signal Transduction
;
Stress, Psychological/*pathology
;
Weight Loss/genetics
;
alpha-MSH/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
