Modulation of the CRH system by substance P/NKA in an animal model of depression.
It has been suggested by studies in animals and humans that substance P (SP) and its receptor neurokinin 1 (NK1R) play an important role in the pathology of depression. The pharmacological blockade or genetic deletion of the NK1 receptor, or the substance P coding gene tac1 led to a decreased emotionality and a reduction of depression-related behaviours in different animal models. In order to characterize molecular changes associated with reduced SP-NK1 signalling in animal models of depression, we assessed the regulation of the CRH system. First, tac1(-/-) animals and tac1(+/+) controls were subjected to bulbectomy, which induces physiological and behavioural changes that are relevant to depression. We demonstrate that tac1(-/-) animals, in contrast to tac1(+/+) controls, do not show anhedonia in the saccharine preference test after bulbectomy. Next, we studied expression levels of CRH, the receptors CRHR1 and CRHR2, and the binding protein CRHBP in the cortex and paraventricular nucleus using real-time RT-PCR. Our results show a strong induction of CRH, CRHBP and CRHR1 expression in the cortex of tac1(-/-), but not in tac1(+/+) animals. In the PVN, bulbectomized tac1(-/-) mice showed an elevated expression of CRHR1 and CRHR2. These results show that substance P/NKA is involved in modulating CRH signalling in an animal model of depression.
Frisch
Pamela
P
Institute of Molecular Psychiatry, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany. pfrisch@uni-bonn.de
Bilkei-Gorzó
András
A
Rácz
Ildiko
I
Zimmer
Andreas
A
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003866:Depressive Disorder / Q000378:metabolism*; D004195:Disease Models, Animal; D005247:Feeding Behavior / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015288:Neurokinin A / Q000378:metabolism*; D009830:Olfactory Bulb / Q000293:injuries / Q000503:physiopathology; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D012439:Saccharin / Q000008:administration & dosage; D013373:Substance P / Q000378:metabolism*; D000099052:CRF Receptor, Type 1
C101531:CRF receptor type 2; D002352:Carrier Proteins; D018019:Receptors, Corticotropin-Releasing Hormone; C067133:corticotropin releasing factor-binding protein; D013373:Substance P; D000099052:CRF Receptor, Type 1; D015288:Neurokinin A; D000324:Adrenocorticotropic Hormone; D012439:Saccharin