Region-specific immediate-early gene expression following the administration of corticotropin-releasing hormone in virgin and lactating rats.
Central administration of corticotropin-releasing hormone (CRH) induces immediate-early gene (IEG) expression (c-fos and NGFI-B) in forebrain structures in a pattern similar to that observed following restraint stress. Lactating rats display modified neuroendocrine and behavioural responses to stress which have been hypothesized to be at least partially mediated through changes within the circuitry converging on the PVN, including CRH activated pathways. Quantitative measures of regional expression of c-fos and NGFI-B mRNA representative of two classical intracellular pathways, were used to define modification of the circuitry involved in the altered response to central CRH in the lactating female. Compared to saline controls, virgin female rats injected with 5 micrograms CRH i.c.v. displayed significantly increased immediate-early gene expression in the hypothalamic paraventricular nucleus (PVN), arcuate nucleus, lateral septum, bed nucleus of the stria terminalis, central, medial and cortical nuclei of the amygdala, and all subfields of the hippocampal formation. In lactating rats treated with CRH there was a significant increase in c-fos gene expression in the CeA and in the hippocampal subfields CA1, CA4 and dentate gyrus but not in the other areas examined. The i.c.v. administration of CRH significantly increased NGFI-B expression in the PVN, arcuate nucleus, medial amygdala and all hippocampal subfields of virgin rats. Lactating rats treated with CRH failed to show a significant increase in NGFI-B expression in the PVN, median eminence, arcuate nucleus, medial amygdala, CA2 and CA3 subfields of the hippocampus. These results further suggest that changes in specific neural circuits might at least partially underlie the modified responses to CRH and perhaps to stress in the lactating female.
Da Costa
A P
AP
Department of Medicine, University of Bristol, Bristol Royal Infirmary, UK.
Kampa
R J
RJ
Windle
R J
RJ
Ingram
C D
CD
Lightman
S L
SL
D000679:Amygdala / Q000502:physiology; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D017781:Genes, Immediate-Early / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism; D017403:In Situ Hybridization; D007276:Injections, Intraventricular; D007774:Lactation / Q000502:physiology*; D008526:Medulla Oblongata / Q000737:chemistry / Q000378:metabolism; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D011149:Pons / Q000737:chemistry / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid / Q000235:genetics; D012686:Septal Nuclei / Q000502:physiology; D012965:Sodium Chloride / Q000494:pharmacology; D013312:Stress, Physiological / Q000503:physiopathology; D013687:Telencephalon / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D012965:Sodium Chloride; D003346:Corticotropin-Releasing Hormone