Cognitive, Behavioral, and Systems NeuroscienceResearch PaperCorticotropin-releasing factor in the nucleus accumbens shell induces swim depression, anxiety, and anhedonia along with changes in local dopamine/acetylcholine balance
Highlights
▶CRF in the NAcS produces swim depression, anhedonia, and anxiety-like behaviors. ▶NAcS CRF markedly increases ACh, which may contribute to these aversive behaviors. ▶NAcS CRF induces an increase in DA that may be related to appetitive behaviors. ▶NAcS CRF may therefore mediate the dual effects of stress through local ACh and DA.
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Subjects and surgery
Male Sprague–Dawley rats (225–350 g, Taconic Farms, Germantown, NY, USA) were individually housed on a reversed 12:12-h light–dark cycle and had ad libitum access to food and water. All tests were conducted between 9:00 and 15:30. Subjects were anesthetized using ketamine (Fort Dodge Animal Health; Overland Park, KS, USA) (80 mg/kg, i.p.) and xylazine (LLOYD Incorporated; Shenandoah, IA, USA) (10 mg/kg, i.p.), supplemented with ketamine when necessary. Stainless steel 21-gauge guide shafts (10
Experiment 1: CRF in the NAcS increases immobility in the forced swim test, while a CRF antagonist blocks CRF-induced swim depression
Histological examination revealed that the injections in each of the experiments were made directly into the shell of the NAc, as illustrated in Fig. 1A. To test the hypothesis that CRF acts in this area to induce depressive-like immobility, rats (n=7–11/group) were given an injection of CRF (10 or 50 ng/side) or vehicle, and their performance in the forced swim test was assessed. As compared with vehicle injection, CRF at both doses in the NAcS significantly increased immobility and decreased
Discussion
The current study assessed the role of extracellular CRF activation in the NAcS, with emphasis placed first on characterizing various behavioral responses induced by CRF and then on determining local neurochemical changes induced by this peptide. Our major findings were that CRF activation in the NAcS: (1) induces depressive-like behaviors such as swim depression and an anhedonic state; (2) elicits anxiety-like behaviors in an elevated plus maze and an open field; and (3) produces a marked and
Conclusions
The results of this study show that activation of the NAcS CRF system produces a variety of aversive emotional responses that occur in association with changes in the local ACh and DA balance. Although a causal relationship has yet to be established, these findings raise the possibility that the aversive behaviors induced by NAcS CRF may be mediated, in part, by changes in ACh and DA, with the ACh aversion system more significantly and persistently activated. They also suggest that the NAcS
Acknowledgments
This research is supported by the E. H. Lane Foundation. We thank Dr. Jean Rivier (The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, San Diego, CA) for kindly providing the D-Phe-CRF (12–41). We also thank Dr. Jessica Barson (The Rockefeller University, NY) for her assistance in preparing this manuscript.
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