Impact of maternal deprivation on brain corticotropin-releasing hormone circuits: prevention of CRH receptor-2 mRNA changes by desipramine treatment.
Corticotropin-releasing hormone (CRH) acts within the brain and pituitary to coordinate the overall endocrinological and behavioral stress response. From postnatal day (PND) 4 to 14, the infant rat displays minimal adrenal response to mild stress. However, maternal deprivation alters the pituitary-adrenal system such that the infants become responsive to specific stimuli. We hypothesized that maternal deprivation would also affect CRH brain circuits. Since tricyclic antidepressants have been shown to decrease the adrenal response to stress in adult rats, we hypothesized that CRH-related changes induced by maternal deprivation would be prevented by this treatment. Thus, we investigated CRH-related molecules on animals that were maternally deprived on PND 13 compared with nondeprived animals. We found that maternal deprivation caused alterations in the gene expression of both CRH receptors (CRHr) 1 and 2 in specific brain regions, and that some of these effects were augmented by chronic isotonic saline injections. There was a significant increase in CRH, CRHr1, and r2 mRNA in the cortex. In amygdala, CRHr1 and r2 mRNAs were decreased. CRHr2 mRNA was also decreased in the ventromedial nucleus of the hypothalamus, whereas an increase was detected in the hippocampal pyramidal cells. One week of desipramine (DES) administration preceding the maternal deprivation event prevented all the deprivation-induced changes in CRHr2 mRNA, regardless of the direction of the original change. We also found that chronic injection treatments enhanced the adrenocortical response and improved the efficiency of negative feedback in maternal deprivation animals. These results demonstrate that maternal deprivation elicits modifications of CRH brain circuits in a site-specific manner, and that the regulation of CRHr2 gene expression is mediated by mechanisms different from those involved with the modulation of CRHr1 in the infant rat.
Vázquez
Delia M
DM
Department of Pediatrics, Endocrine Division, University of Michigan, 1150 West Medical Center Drive, 8346 Medical Science Research Building III, Ann Arbor, MI 48109-0646, USA. dmvazq@umich.edu
Eskandari
Ramin
R
Phelka
Andrew
A
López
Juan F
JF
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis*; D003891:Desipramine / Q000494:pharmacology*; D005260:Female; D008297:Male; D008426:Maternal Deprivation; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000096:biosynthesis*
C101531:CRF receptor type 2; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone; D003891:Desipramine