PT  - JOURNAL ARTICLE
AU  - Paula J. Brunton
AU  - Simone L. Meddle
AU  - Shuaike Ma
AU  - Tomasz Ochedalski
AU  - Alison J. Douglas
AU  - John A. Russell
TI  - Endogenous Opioids and Attenuated Hypothalamic-Pituitary-Adrenal Axis Responses to Immune Challenge in Pregnant Rats
AID  - 10.1523/JNEUROSCI.0866-05.2005
DP  - 2005 May 25
TA  - The Journal of Neuroscience
PG  - 5117--5126
VI  - 25
IP  - 21
4099  - http://www.jneurosci.org/content/25/21/5117.short
4100  - http://www.jneurosci.org/content/25/21/5117.full
SO  - J. Neurosci.2005 May 25; 25
AB  - In late pregnant rats, the hypothalamic-pituitary-adrenal (HPA) axis is hyporesponsive to psychogenic stressors. Here, we investigated attenuated HPA responses to an immune challenge and a role for endogenous opioids. ACTH and corticosterone were assayed in blood samples from virgin and 21 d pregnant rats before and after endotoxin [lipopolysaccharide (LPS); 1 μg/kg, i.v.], interleukin-1β (IL-1β; 500 ng/kg, i.v.), or vehicle. In virgins, plasma ACTH concentrations increased 1 h after LPS and 15 min after IL-1β, as did corticosterone, with no responses in pregnant rats. In situ hybridization revealed increased corticotrophin releasing hormone (CRH) mRNA expression in the dorsomedial parvocellular paraventricular nucleus (pPVN) and increased anterior pituitary pro-opiomelanocortin mRNA expression 4 h after IL-1β in virgins; these responses were absent in pregnant rats. In contrast, immunocytochemistry showed that Fos expression was similarly increased in the nucleus tractus solitarius (NTS) A2 region in virgin and pregnant rats 90 min and 4 h after IL-1β. Naloxone pretreatment (5 mg/kg, i.v.) restored ACTH and pPVN CRH mRNA responses after IL-1β in pregnant rats but reduced the CRH mRNA response in virgins without affecting ACTH. Proenkephalin-A and μ-opioid receptor mRNA expression in the NTS was significantly increased in the pregnant rats, indicating upregulated brainstem opioid mechanisms. IL-1β increased noradrenaline release in the PVN of virgin, but not pregnant, rats. However, naloxone infused directly into the PVN increased noradrenaline release after IL-1β in pregnant rats. Thus, the HPA axis responses to immune signals are suppressed in pregnancy at the level of pPVN CRH neurons through an opioid mechanism, possibly acting by preterminal autoinhibition of NTS projections to the pPVN.